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Module 12. Psychiatric Disorders

The following common psychiatric disorders are discussed within this module:

Major depressive disorder
Bipolar disorder
Anxiety disorders
Sleep disorders
Eating disorders
Schizophrenia
Substance abuse

Introduction

Psychiatric disorders are a major public health concern, affecting about 25% of adults in the United States.¹ These disorders can have a significant negative impact on an individual's quality of life and daily functioning. Depending on the severity, some psychiatric disorders can also be associated with significant mortality. In addition, psychiatric disorders can have a significant economic burden on society, including the cost of medical care, lost productivity, and costs associated with disabilities.

MAJOR DEPRESSIVE DISORDER

Overview

Major depressive disorder (MDD) is a common psychiatric condition. Epidemiologic studies have estimated the lifetime prevalence of MDD to be between 13% and 16%, with 12-month estimates of 5% to 6%.^2,3 The cause of MDD remains unknown but it is generally thought to be linked to altered or depleted levels of neurotransmitters in the brain—specifically serotonin, dopamine, and norepinephrine.⁴Other factors can also contribute to the development of MDD, including genetics, childhood or early life trauma, family history, and stressful life events.^4,5 The most common signs and symptoms associated with MDD are listed in Table 1.

Table 1. Criteria for Diagnosis of Major Depressive Disorder
Diagnostic and Statistical Manual of Mental Disorders-5⁵

Depressed mood most of the day
Loss of interest in or pleasure from activities
Change in weight (significant loss or gain) or appetite
Insomnia or excess sleeping
Fatigue or loss of energy
Psychomotor agitation or retardation
Decreased ability to concentrate or think
Thoughts of death or suicide
Feelings of worthlessness or guilt

The Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5), provides specific criteria for the diagnosis of MDD (see Table 1).⁵ Five or more of the symptoms listed in Table 1 must be present daily or nearly every day for a 2-week period, represent a change from previous behavior or functioning, and have a significant impact on social, work, or other areas of functioning. In addition, a number of rating scales are available to assess the severity of MDD.⁶ These include the Hamilton Rating Scale for Depression (HAM-D), the Beck Depression Inventory (BDI), and the Montgomery-Asberg Depression Rating Scale (MADRS). These scales generally consist of clinician- or patient-rated questions or items and provide a numeric scoring of MDD severity.

Major depressive disorder is a leading risk factor for suicide, which is 20 times more common among patients with MDD than among those without depression.^7,8 The presence of other risk factors, such as a chronic physical illness, substance abuse, childhood traumas, or family history of suicide, may have an additive effect. Because of this, patients with depression should be evaluated for risk of suicide or self-harm.⁹The American Psychiatric Association (APA) lists the following factors to consider when assessing suicide risk for patients with MDD: history of prior suicide attempts, history/presence of suicidal ideation, access to means for committing suicide, aggressive or violent behavior, alcohol or substance use, disabling medical illness, family history of suicide, childhood traumas, and recent psychiatric hospitalizations.

Treatment Recommendations

The primary goal of treatment of MDD is resolution of acute symptoms of depression and prevention of relapse of symptoms.¹⁰ Treatment of MDD is generally divided into 3 phases: acute, continuation, and maintenance.^9,11During the acute phase of treatment (6 to 10 weeks), remission of symptoms is the goal, along with a return to normal activities. For the continuation phase (6 to 9 months), prevention of relapse is the goal. For the maintenance phase (12 to 36 months), treatment is continued to reduce the risk of recurrence. Some patients may require life-long maintenance therapy to prevent recurrent episodes of depression. The APA guidelines on MDD provide recommendations for treatment during the acute, continuation, and maintenance phases, using both nonpharmacologic and pharmacologic therapies.⁹

Nonpharmacologic therapy

Electroconvulsive therapy (ECT) and psychotherapy are the 2 main nonpharmacologic therapies used in the treatment of MDD. Electroconvulsive therapy is generally reserved for patients with severe MDD not responsive to pharmacologic therapies, for patients where a rapid response is needed (e.g., suicidal patients), or for those with psychotic symptoms in addition to MDD.^9,11

Psychotherapy consists of cognitive behavioral therapy, interpersonal therapy, and problem-solving therapies. Psychotherapy may be an effective choice when psychosocial stressors or interpersonal difficulties are present.⁹ For some patients, such as women who are or wish to become pregnant or are breastfeeding, psychotherapy may be the initial treatment of choice, depending on the severity of depression. In some cases, psychotherapy may be combined with pharmacologic therapy, such as for patients with moderate to severe MDD.

Pharmacologic therapy

The APA recommends pharmacologic therapy with antidepressants as initial therapy for most patients with mild to moderate MDD, as well as for patients with severe MDD unless treatments such as ECT are used.⁹ No one class of antidepressants is preferred for initial treatment since all are considered effective. However, use of selective serotonin reuptake inhibitors (SSRIs), serotonin norepinephrine reuptake inhibitors (SNRIs), mirtazapine, or bupropion may be appropriate for most patients.^12,13 Otherwise, selection of an antidepressant may be based on the agent's side effect profile, potential for drug interactions, patient use history, and cost.^12,13 Certain agents, specifically monoamine oxidase inhibitors, should be reserved for patients not responding to other antidepressants, primarily due to their risk of drug interactions and required dietary restrictions. The various available antidepressants, their common side effects, and risk for drug interactions are described in Table 2.

Table 2. Oral Medications Used for Psychiatric Disorders^11-14,18*
Medication (dosage forms)	Use/adult initial dose as mg/d (range as mg/d)	Common side effects	Common drug interactions	Comments
Tricyclic antidepressants
Amitriptyline (10, 25, 50, 75, 100, 150 mg tablets)	Depression: 25 to 50 mg as a single dose at bedtime or in divided doses (100 to 300 mg in divided doses)	Dry mouth, blurred vision, urinary retention, weight gain, tachycardia, sedation, postural hypotension, dizziness, headache	Increased plasma concentrations of TCAs when given with CYP2D6 inhibitors; dose adjustment of TCA may be necessary Risk of serotonin syndrome increased when given with other serotonergic agents Avoid use within 14 days of MAOIs due to the potential for hypertensive crisis Serum concentrations of carbamazepine may be increased and that of TCAs decreased with concurrent use TCAs may enhance the CNS depressant effects of alcohol, barbiturates, and other CNS depressants Increased risk of CNS toxicity and serotonin syndrome with concurrent linezolid	Box warning regarding suicidal thinking and behavior (suicidality) in children, adolescents, and young adults for all antidepressants
Clomipramine (25, 50, 75 mg capsules)	OCD: 25 mg (100 to 250 mg)
Desipramine (10, 25, 50, 75 100, and 150 mg tablets)	Depression: 25 to 50 mg in single or divided doses (100 to 300 mg in divided doses)
Imipramine (10, 25, 50 mg tablets; 75, 100, 125, 150 mg capsules)	Depression: 75 mg (50 to 200 mg as a single bedtime dose or in divided doses)
Nortriptyline (10, 25, 50, 75 mg capsules; 10 mg/5 mL oral solution)	Depression: 75 to 100 mg (150 mg in single or divided doses)
Tetracyclic antidepressants
Maprotiline (25, 50, and 75 mg tablets)	Depression: 25 to 75 mg in single or divided doses (75 to 150 mg in single or divided doses)	Sedation, increased appetite, weight gain, dizziness, dry mouth, constipation	Increased serum concentrations with concurrent CYP inhibitors Decreased serum concentrations with concurrent CYP inducers Avoid use within 14 days of MAOIs due to the potential for hypertensive crisis Increased risk of CNS toxicity and serotonin syndrome with concurrent linezolid	Box warning regarding suicidal thinking and behavior (suicidality) in children, adolescents, and young adults for all antidepressants
Mirtazapine (7.5, 15, 30, 45 mg tablets; 15, 30, 45 mg orally disintegrating tablets)	MDD: 15 mg nightly (15 to 45 mg)
Selective serotonin reuptake inhibitors
Citalopram (10, 20, 40 mg tablets; 2 mg/mL oral solution)	Depression: 20 mg (20 to 40 mg) Maximum dose is 20 mg/day if taken concurrently with CYP2C19 inhibitors (e.g., omeprazole)	Nausea, diarrhea, headache, insomnia, nervousness, restlessness, dry mouth, somnolence	Dose adjustments may be needed when SSRIs are given concurrently with drugs metabolized by CYP2D6 Serum concentrations of some SSRIs may be altered by concurrent use with CYP2D6 inhibitors or inducers Serum concentrations of some SSRIs may be altered by concurrent use with strong CYP2C19 inhibitors or inducers Increased risk of serotonin syndrome when SSRIs are given concurrently with other serotonergic drugs Avoid SSRI use within 14 days of MAOIs due to the potential for hypertensive crisis Concurrent use of SSRIs with antiplatelet agents may increase risk of bleeding	Box warning regarding suicidal thinking and behavior (suicidality) in children, adolescents, and young adults for all antidepressants Metabolic pathways of the SSRIs: Citalopram and escitalopram: CYP2C19 and CYP3A4 Fluoxetine: CYP2D6 and CYP2C9 Paroxetine: CYP2D6 Sertraline: CYP2C19 Both fluoxetine and paroxetine are considered strong inhibitors of CYP2D6
Escitalopram (5, 10, 20 mg tablets; 1 mg/mL oral solution)	MDD: 10 mg (10 to 20 mg) GAD: 10 mg (10 to 20 mg)
Fluoxetine (10, 20, 40 mg capsules; 60 mg tablets; 90 mg delayed release capsules; 20 mg/5 mL oral solution)	MDD: 20 mg (20 to 80 mg) OCD: 20 mg (20 to 80 mg) Panic disorder: 10 mg (10 to 60 mg) Bulimia nervosa: 60 mg Treatment-resistant MDD (with olanzapine): 20 to 50 mg
Fluvoxamine (25, 50, 100 mg tablets; 100, 150 ER capsules)	OCD: 50 to 100 mg at bedtime (100 to 300 mg)
Paroxetine (10, 20, 30, 40 mg tablets; 12.5, 25, 37.5 mg controlled release tablets; 10 mg/5 mL oral suspension)	MDD: 20 mg (20 to 50 mg) GAD: 20 mg (20 to 50 mg) OCD: 20 mg (20 to 60 mg) Panic disorder: 10 mg (10 to 60 mg) Social anxiety disorder: 20 mg (20 to 60 mg) PTSD: 20 mg (20 to 50 mg)
Sertraline (25, 50, 100 mg tablets; 20 mg/mL oral concentrate)	MDD: 50 mg (50 to 200 mg) OCD: 50 mg (50 to 200 mg) Panic disorder: 25 mg (50 to 200 mg) SAD: 25 mg (50 to 200 mg) PTSD: 25 mg (50 to 200 mg)
Serotonin norepinephrine reuptake inhibitors
Desvenlafaxine (25, 50, 100 mg ER tablets)	MDD: 50 mg	Anxiety, constipation, decreased appetite, dizziness, insomnia, nausea, somnolence, hyperhidrosis Sustained hypertension (10 to 15 mmHg in systolic blood pressure) Serum cholesterol elevations	Concurrent use with potent CYP3A4 inhibitors may increase serum concentrations of desvenlafaxine	Box warning regarding suicidal thinking and behavior (suicidality) in children, adolescents, and young adults for all antidepressants For all SNRIs: Increased risk of serotonin syndrome with serotonergic drugs Avoid use within 14 days of MAOIs due to the potential for hypertensive crisis Concurrent use with TCAs may result in increases in TCA serum concentrations and toxicity Concurrent use with antiplatelets/ anticoagulants may increase risk of bleeding
Duloxetine (20, 30, 60 mg ER capsules)	MDD: 40 to 60 mg GAD: 60 mg (60 to 120 mg)		Avoid coadministration with strong CYP1A2 and CYP2D6 inhibitors; concurrent use may increase serum concentrations of duloxetine and require dose adjustments
Levomilnacipran (20, 40, 80,120 mg ER capsules)	Depression: 20 mg (40 to 120 mg)		Concurrent use with strong CYP3A4 inhibitors (ketoconazole, clarithromycin, ritonavir) may increase serum concentrations of levomilnacipran; do not exceed 80 mg/d if used with these agents
Venlafaxine (25, 37.5, 50, 75, 100 mg tablets)	MDD: 37.5 to 75 mg in divided doses (75 to 375 mg in divided doses)		Increases in venlafaxine serum concentrations with azole antifungal agents and cimetidine May increase serum concentrations of haloperidol, requiring dose adjustments
Venlafaxine ER (37.5, 75, 150, 225 mg tablets; 37.5, 75, 150 mg capsules)	MDD: 37.5 to 75 mg (75 to 225 mg) Panic disorder: 37.5 mg (75 to 225 mg) SAD: 75 mg GAD: 37.5 to 75 mg (75 to 225 mg)
MAOIs
Isocarboxazid (10 mg tablets)	Depression: 20 mg in divided doses twice daily (20 to 60 mg in divided doses)	Sleep disturbance, orthostatic hypotension, sexual dysfunction, weight gain	Use of MAOIs with serotonergic drugs, bupropion, sympathomimetics, and tyramine-rich food may cause hypertensive crisis At least 2 weeks should elapse between MAOI discontinuation and use of these agents or foods	Box warning regarding suicidal thinking and behavior (suicidality) in children, adolescents, and young adults for all antidepressants
Phenelzine (15 mg tablets)	Depression: 45 mg in divided doses three times daily (45 to 90 mg in divided doses)
Tranylcypromine (10 mg tablets)	MDD: 10 mg (30 to 60 mg in divided doses)
Miscellaneous
Bupropion (75 and 100 mg tablets)	MDD: 200 mg in divided doses twice daily (300 mg in divided doses)	Agitation, anxiety, insomnia, headache, nausea, anorexia Dose-related seizures may occur	Metabolism may be induced by agents such as carbamazepine, phenobarbital, and phenytoin CYP2B6 inhibitors may increase bupropion serum levels; dose adjustments may be needed if inhibitors are discontinued Severe hypertension has been reported with concurrent use of bupropion and nicotine Bupropion may inhibit metabolism of CYP2D6 substrates; dose reductions of the substrates may be needed	Box warning regarding suicidal thinking and behavior (suicidality) in children, adolescents, and young adults for all antidepressants For all miscellaneous antidepressants: Increased risk of serotonin syndrome with serotonergic drugs Avoid use within 14 days of MAOIs due to the potential for hypertensive crisis Concurrent use with antiplatelets/ anticoagulants may increase risk of bleeding
Bupropion ER/XL (100, 150, 200 mg 12-hour ER tablets; 150, 300, 450 mg 24-hour ER tablets; 174, 348, 522 mg 24-hour ER tablets)	MDD: 12-hour ER tablets: 400 mg; 24-hour ER tablets: 300 mg (300 to 450 mg) or 522 mg
Nefazodone (50, 100, 150, 200, 250 mg tablets)	Depression: 200 mg in divided doses twice daily (300 to 600 mg in divided doses)	Somnolence, dry mouth, nausea, dizziness Rarely hepatic failure	Coadministration of nefazodone and carbamazepine should be avoided due to reductions in nefazodone and increases in carbamazepine serum concentrations Plasma concentrations of CYP3A4 substrates may be elevated with concurrent nefazodone administration
Trazodone (50, 100, 150, 300 mg tablets; 150, 300 mg ER tablets)	Depression: 150 mg in divided doses; (150 to 400 mg in divided doses)	Drowsiness, orthostatic hypotension, priapism	Coadministration with azole antifungal agents may result in increases in trazodone serum concentrations; dose adjustments may be needed Coadministration of trazodone and carbamazepine may result in reductions in trazodone and increases in carbamazepine serum concentrations Macrolides may cause increases in serum concentrations of trazodone; dose adjustments may be needed
Vilazodone (10, 20, 40 mg tablets)	MDD: 10 mg (20 to 40 mg)	Diarrhea, insomnia, dizziness, fatigue, dry mouth	Concurrent use with CYP3A4 inducers may result in decreased systemic exposure to vilazodone Concurrent use with CYP3A4 inhibitors may increase exposure to vilazodone
Vortioxetine (5, 10, 20 mg tablets)	MDD: 10 mg (10 to 20 mg)	Nausea, abnormal dreams, dizziness, constipation, diarrhea, vomiting, dry mouth	Concurrent use with bupropion may require a 50% dose reduction for vortioxetine Strong CYP2D6 inhibitors may increase serum concentrations of vortioxetine; a 50% reduction in vortioxetine dose may be needed Strong CYP3A4 inducers may decrease serum concentrations of vortioxetine, requiring higher doses of the antidepressant
Second-generation antipsychotics
Aripiprazole (2, 5, 10, 15, 20 mg tablets; 10, 15 mg orally disintegrating tablets)	MDD: 2 to 5 mg (2 to 15 mg) Schizophrenia: 10 to 15 mg (10 to 30 mg) Bipolar I disorder: 10 to 15 mg (up to 30 mg)	Anxiety, headache, nausea, constipation, lightheadedness, agitation, akathisia Lower risk of metabolic effects (diabetes, weight gain, hyperlipidemia) or prolactin elevations than other SGAs	Dose adjustments may be needed if given concurrently with strong CYP3A4 (ketoconazole, clarithromycin) or 2D6 inhibitors (fluoxetine, paroxetine, or quinidine) or with 3A4 inducers (carbamazepine, phenobarbital, phenytoin, or rifampin)	Box warning for all antipsychotics regarding Increased mortality in elderly patients with dementia-related psychosis Additional box warnings with clozapine regarding agranulocytosis, myocarditis, orthostatic hypotension, bradycardia, syncope, seizures, myocarditis and cardiomyopathy; weekly monitoring of white blood cells is required for all patients for the first 6 months of treatment Clozapine is only available through a restricted access program Relative adverse metabolic effects for SGAs: Diabetes: clozapine, olanzapine > paliperidone, quetiapine, risperidone, iloperidone> asenapine>>lurasidone, ziprasidone, aripiprazole Weight gain: clozapine, olanzapine> paliperidone, quetiapine, risperidone> asenapine, iloperidone> aripiprazole> lurasidone, ziprasidone Elevated prolactin levels: Risperidone, paliperidone> asenapine> olanzapine, ziprasidone> aripiprazole, clozapine, iloperidone, lurasidone, quetiapine
Asenapine (5, 10 mg SL tablet)	Bipolar disorder: 10 to 20 mg as divided doses Schizophrenia: 10 mg (10 to 20 mg) as divided doses	Insomnia, somnolence, nausea, vomiting, weight gain, orthostatic hypotension	Serum concentrations of asenapine may be increased by concurrent use with CYP1A2 inhibitors
Brexpiprazole (0.25, 0.5, 1, 2, 3, 4 mg tablet)	MDD: 0.5 to 1 mg (2 to 3 mg) Schizophrenia: 1 mg (2 to 4 mg)	Akathisia, weight gain, increased triglycerides	Strong CYP2D6 inhibitors: administer one-half the usual dose (in schizophrenia) Strong CYP3A4 inhibitors: administer one-half the usual dose Moderate/strong CYP2D6 inhibitors in combination with moderate/strong CYP3A4 inhibitors: administer one-fourth the usual dose Strong CYP3A4 inducers: double the usual dose over 1 to 2 weeks
Cariprazine (1.5, 3, 4.5, and 6 mg capsules)	Bipolar disorder: 1.5 mg (3 to 6 mg) Schizophrenia: 1.5 mg (1.5 to 6 mg)	Akathisia, extrapyramidal reactions, headache, insomnia, parkinsonian-like syndrome, nausea, vomiting	Concurrent CYP3A4 inhibitors or inducers: dosage adjustments are needed
Clozapine (25, 50, 100, 200 mg tablets; 12.5, 25, 100, 150, 200 mg orally disintegrating tablets; 50 mg/mL oral suspension)	Treatment-resistant schizophrenia or recurrent suicidal behavior: 12.5 mg once or twice daily titrated by 25 to 50 mg/d to a target dose of 300 to 450 mg/d given in divided doses (300 to 900 mg as divided doses)	Granulocytopenia or agranulocytosis Dose-related seizures Increased salivation and enuresis Gastrointestinal motility, sedation, diabetes, weight gain, hyperlipidemia Potentially fatal myocarditis	Dose adjustments may be needed if given concurrently with strong CYP3A4 (ketoconazole, clarithromycin) or CYP1A2 inhibitors (fluvoxamine) CYP1A2 inducers (carbamazepine, omeprazole, rifampin) may reduce clozapine serum concentrations
Iloperidone (1, 2, 4, 6, 8, 10,12 mg tablets)	Schizophrenia: 2 mg as divided doses (12 to 24 mg as divided doses)	Orthostatic hypotension, QT prolongation, dizziness, somnolence, dry mouth, weight gain	CYP2D6 inhibitors (fluoxetine, paroxetine, or quinidine) may increase serum concentrations of iloperidone; dose reductions may be needed
Lurasidone (20, 40, 80, 120 mg tablets)	Bipolar disorder depression: 20 mg (20 to 120 mg) Schizophrenia: 40 mg (40 to 160 mg)	Akathisia, nausea, extrapyramidal symptoms, agitation, somnolence	Dosage should not exceed 80 mg/day when given with a moderate CYP3A4 inhibitor Do not use with strong CYP3A4 inhibitors or inducers
Olanzapine (2.5, 5, 7.5, 10, 15, 20 mg tablets; 5, 10, 15, 20 mg orally disintegrating tablets)	Bipolar disorder: 10 to 15 mg (5 to 20 mg) Schizophrenia: 5 to 10 mg (10 to 20 mg) Treatment-resistant MDD (with fluoxetine): 5 to 20 mg	Weight gain and metabolic effects (e.g., diabetes and hyperlipidemia), postural hypotension, somnolence, constipation, dizziness, akathisia	Dose adjustments may be needed if given concurrently with strong CYP1A2 inhibitors (fluvoxamine) CYP1A2 inducers (carbamazepine, omeprazole, rifampin) may reduce olanzapine serum concentrations
Paliperidone (1.5, 3, 6, 9 mg ER tablets)	Schizophrenia: 6 mg (3 to 12 mg)	Extrapyramidal symptoms, elevation of prolactin concentrations, nausea, somnolence, dizziness, tachycardia, QT prolongation	Dose adjustments may be needed if given concurrently with strong CYP3A4 inducers (carbamazepine, phenobarbital, phenytoin, or rifampin) CYP2D6 inhibitors (fluoxetine, paroxetine, or quinidine) may decrease serum concentrations of paliperidone
Quetiapine (25, 50, 100, 150, 200, 300, 400 mg tablets)	Bipolar disorder acute mania: 100 mg in divided doses (400 to 800 mg as divided doses) Bipolar disorder depression: 50 mg (300 mg at bedtime) Schizophrenia: 50 mg as divided doses (150 to 750 mg as divided doses)	Somnolence, dizziness, constipation, postural hypotension, hyperglycemia, weight gain	Dose adjustments may be needed if given concurrently with strong CYP3A4 inhibitors (ketoconazole, clarithromycin)
Quetiapine XR (50, 150, 200, 300, 400 mg ER tablets)	MDD: 50 mg (300 mg) Schizophrenia: 300 mg (400 to 800 mg) Bipolar disorder acute mania: 300 mg (400 to 800 mg) Bipolar disorder depression: 50 mg (300 mg)
Risperidone (0.25, 0.5, 1, 2, 3, 4 mg tablets; 0.25, 0.5, 1, 2, 3, 4 mg orally disintegrating tablets; 1 mg/mL oral solution)	Bipolar mania: 2 to 3 mg (1 to 6 mg) Schizophrenia: 2 mg (4 to 8 mg)	Postural hypotension, insomnia, constipation, dizziness, prolactin elevation, hyperglycemia, weight gain	Serum concentrations may be increased if given concurrently with CYP2D6 inhibitors (fluoxetine, paroxetine, quinidine)
Ziprasidone (20, 40, 60, 80 mg capsules)	Bipolar I disorder: 80 mg as divided doses (80 to 160 mg as divided doses) Schizophrenia:40 mg as divided doses (40 to 200 mg as divided doses)	Somnolence, QT prolongation, extrapyramidal symptoms, paradoxical excitement	Avoid concurrent use with drugs that may prolong the QT interval Dose adjustments may be needed if given concurrently with strong CYP3A4 inhibitors (ketoconazole, clarithromycin) due to increased antipsychotic serum levels
Mood stabilizers
Lithium carbonate (150, 300, 600 mg capsules; 300 mg tablets; 300, 450 mg ER tablets)	900 to 1800 mg in divided doses: both initial and maintenance dosing	Nausea and fatigue with initial therapy Tremor, thirst, polyuria, edema, weight gain may persist Confusion, ataxia Nephrogenic diabetes insipidus Hypothyroidism with long-term use	Avoid use with NSAIDs, ACE inhibitors, diuretics since these may increase lithium serum concentrations Theophylline and caffeine may lower lithium serum concentrations	Therapy is monitored by serum concentrations, with 0.6 to 1 mEq/L for maintenance therapy and 0.8 to 1.2 mEq/L for acute treatment
Carbamazepine (100, 200, 300, 400 mg tablets; 100, 200 mg chewable tablets; 100 mg/5 mL oral suspension; 100, 200, 300 mg ER capsules; 100, 200, 400 mg ER tablets)	400 mg in divided doses (400 to 1600 mg in divided doses)	Rash, dizziness, diplopia, nausea, somnolence, headache, hyponatremia	Acts as a strong inducer of CYP3A4; substrate dosage adjustments may be needed Inhibitors of CYP3A4 may decrease carbamazepine metabolism and increase serum concentrations	Box warnings for aplastic anemia and agranulocytosis and risk of serious dermatologic reactions (including TEN and SJS), especially among individuals with HLA-B*1502 allele
Lamotrigine (25, 100, 150, 200 mg tablets; 2, 5, 25 mg chewable tablets; 25, 50, 100, 200 mg orally disintegrating tablets; 25, 50, 100, 200, 250, 300 mg ER tablets)	Follow dose titration in package labeling	Nausea, dizziness, somnolence Mild rash occurs in about 10% of patients A small percentage may experience severe, life-threatening rash	Other anticonvulsants (carbamazepine, phenytoin, phenobarbital) can reduce lamotrigine serum concentrations by as much as 40% Concurrent use with valproate may increase serum concentrations of lamotrigine by reducing lamotrigine clearance; dose reductions of lamotrigine may be required Drugs that induce or inhibit glucuronidation may alter lamotrigine clearance; dose adjustments may be needed	Box warning for serious, life-threatening skin rashes (including SJS), occurring within 2 to 8 weeks of starting therapy Slow dose titration may reduce the risk of rash
Valproic acid (125, 250, 500 mg capsules)	750 mg in divided doses; increase dose as rapidly as possible to achieve the lowest therapeutic dose that produces the desired clinical effect or appropriate plasma concentration	Somnolence, fatigue, weight gain, nausea, diarrhea, tremor Reversible hair loss Dose-related thrombocytopenia Transient elevations of liver enzymes	Acts as a moderate inhibitor of CYP2C9; substrate dosage adjustment may be needed	Box warnings for hepatotoxicity with fatalities, risk of teratogenicity, and life-threatening pancreatitis

Once treatment with an antidepressant has been initiated, between 4 and 8 weeks of treatment is needed to fully assess response.⁹If response is not adequate after this time (at an adequate dosage), a different antidepressant may be tried, either from the same or a different pharmacologic class. Alternatively, a second antidepressant from a different class may be added.¹¹ Once a response has been achieved in the acute phase, treatment with the same antidepressant should be carried over to the continuation phase. For those patients requiring maintenance therapy, the antidepressant that induced symptom remission is the first-line choice.¹¹Patients who do not respond after receiving 2 or more appropriate medication trials may require adjunctive therapy, for example a second-generation antipsychotic (SGA; e.g., aripiprazole or olanzapine), lithium, or lamotrigine.^9,11

Special Populations

Pregnant or breastfeeding women

For women with MDD who are pregnant, the risk of treatment must be weighed against the risk of not treating the depression, since depression itself may have an adverse effect on the fetus.^14,15Treatment choice will depend on the severity of symptoms and the risk for self-harm by the patient.¹⁶ In some cases, nonpharmacologic therapy may be appropriate.¹⁵ If antidepressants are used during pregnancy, women should be counseled for the potential risk to the fetus. Monotherapy is preferred, with the lowest effective dose used.¹⁴ In addition, first trimester exposure should be avoided, if possible.

Antidepressants may also cross into human breast milk.¹⁵ Based on information from the most recent statement from the American Academy of Pediatrics on drug transfer into breast milk, several antidepressants (including citalopram, fluoxetine, mirtazapine, sertraline, venlafaxine, and nortriptyline) may result in infant serum concentrations more than 10% of maternal levels. The effects of these agents on infant growth and long-term neurodevelopment are not known.¹⁷

Monitoring Parameters

Many of the antidepressants are associated with significant adverse events that may interfere with patient adherence to therapy. Additionally, response to treatment may not be seen for several weeks after initiating treatment.¹¹ Some antidepressants may have the potential for drug interactions based on their route of metabolism or from additive pharmacologic effects. Information on common adverse events and drug interactions with the antidepressants is summarized in Table 2.

Patient Case #1

A physician has contacted you to discuss possible therapeutic options to treat depression in one of her patients, LW, a 32-year-old female. In discussion with the physician you learn that the patient has lost 20 pounds in the last 2 months, has no interest in her usual activities, and spends most of her day sleeping.

Her current medical conditions include the following:

Hypertension (currently well controlled)
Gastroesophageal reflux disease
Seasonal allergic rhinitis

Past medical history

Seizures secondary to anorexia nervosa during adolescence

LW's medication history includes:

Hydrochlorothiazide 25 mg daily
Omeprazole 20 mg daily
Nasonex as needed

Which of the following treatment options would be most appropriate for LW at this time?

Citalopram 40 mg once daily
Venlafaxine 150 mg once daily
Bupropion 200 mg daily in divided doses
Sertraline 50 mg once daily

(Response D is correct; it will not exacerbate the patient's hypertension (unlike venlafaxine) and is the least likely to interact with omeprazole (unlike citalopram). Also, the patient has a past history of seizure disorder, a relative contraindication to bupropion.)

Your recommendation for treatment was accepted by the physician. Two weeks later, the patient returns to your pharmacy to discuss her treatment and how it is working. While she is feeling better, she still does not feel like her "old self". LW asks if you can call her physician to discuss increasing the dose of her antidepressant or maybe switching to another agent. Which of the following is the best course of action for you to take regarding LW's treatment?

The antidepressant medication LW is taking should have exerted its full effect by now. You call her physician and recommend that LW's current dose of medication should be doubled.
Although her medication should not be changed at this point, LW is in need of nonpharmacologic therapy, such as ECT. You call her physician to discuss these nonpharmacologic interventions.
Antidepressant medications do not exert their full effect for 4 to 8 weeks. After checking her medication profile, you assure LW that the dose is appropriate for her at this time and no change is necessary.
LW is likely resistant to treatment with antidepressants and requires adjunctive therapy. You call the physician to recommend the addition of aripiprazole.

(Response C is correct. Antidepressants take 4 to 8 weeks before a full effect is seen. LW has had some improvement after only 2 weeks, indicating that the medication is having a beneficial effect.)

BIPOLAR DISORDER

Overview

The frequency of bipolar disorder (BPD) has been estimated to be about 1% for bipolar I disorder (BPD-I) and 1.1% for bipolar II disorder (BPD-II) as a lifetime prevalence.¹⁸ No difference in the frequency of BPD has been seen between men and women nor between different racial/ethnic or socioeconomic groups. Similar to MDD, the exact pathophysiology of BPD is unknown.¹⁹ Although a disruption of neurotransmitters has been suggested for the pathophysiology of BPD, changes in synaptic functioning are thought to be a more likely cause of BPD symptoms, along with anatomic abnormalities in various areas of the brain and genetic and environmental factors.^19,20 Episodes of elevated mood are the classic symptom of BPD.¹⁸ These are often accompanied by manic symptoms (Table 3). If these manic episodes occur without seriously impaired judgment, it is considered hypomania.¹⁹ Mania can alternate with episodes of depression with or without episodes of normal mood inbetween.²⁰ An episode is considered mixed when symptoms of both mania and depression are present.¹⁹

The DSM-5 provides specific criteria for the diagnosis of BPD (see Table 3).⁵ These criteria distinguish between 2 major types of BPD, BPD-I and BPD-II. The major difference between these types of BPD is the severity of manic episodes. In BPD-I, mania or hypomania is present, while in BPD-II, the episodes of elevated mood are hypomanic. In both types, patients also experience depressive episodes, but the episodes are not mixed in BPD-II.¹⁹ Severity of illness can be assessed with a number of rating scales, including HAM-D and BDI for depressive symptoms and instruments specific for mania, such as the Young Mania Rating Scale (YMRS) and the Mood Disorder Questionnaire (MDQ).⁶

Table 3. Criteria for Diagnosis of Bipolar Disorder Diagnostic and Statistical Manual of Mental Disorders-5⁵
Bipolar-I disorder	Bipolar-II disorder
Manic/hypomanic episodes Abnormally/persistently elevated mood for at least 1 week nearly all day every day Inflated self-esteem Decreased need for sleep Excessively talkative Flight of ideas Easily distracted Increased goal-directed activities Risky behaviors Behavior impairs social/work functioning No other physiological causes present	Hypomanic episodes Abnormally/persistently elevated mood on at least 4 consecutive days nearly all day every day Manic symptoms as with BPD-I Symptoms are noticeable but not severe enough to cause impairment of social/work functioning No other physiological causes present
Depressive episodes	Depressive episodes
As for MDD (see Table 1)	As for MDD (see Table 1)
BPD-I = bipolar disorder I; MDD = major depressive disorder.

Treatment Recommendations

The primary goal of therapy for BPD is to control acute symptoms and prevent recurrences that could impair patient daily functioning and increase the risk of self-harm or even suicide.¹⁸ Initial therapy is based on presenting symptoms, either mania/hypomania or depression. Treatment recommendations for BPD have been published by the APA as well as the Texas Department of State Health Services.¹⁸These guidelines provide information on both the acute and maintenance treatment of BPD, presented as an algorithm based on patient symptoms and response to initial therapy. Both guidelines were last updated many years ago; therefore, newer agents are not specifically discussed.

Nonpharmacologic therapy

Nonpharmacologic therapies, often in conjunction with pharmacologic agents, have been used for treatment of BPD. Often patients with BPD have comorbid conditions that may affect treatment for BPD.²¹ Cognitive-behavioral therapies, family-focused therapies, and other psychosocial treatments have been shown to have some efficacy in the treatment of BPD.

Pharmacologic therapy

Initial treatment for BPD will depend in part on the presenting symptoms. Treatment generally consists of mood stabilizers (lithium and certain anticonvulsants), SGAs, and antidepressants (see Table 2).

For patients with mania, mood stabilizers (lithium or valproic acid) or SGAs (for example, aripiprazole, quetiapine, risperidone, or ziprasidone) may be considered as monotherapy.^18,22 Subsequent therapy is dependent on patient response. For patients not responding to initial monotherapy, a different agent (either another mood stabilizer or SGA) may be tried. A two-drug regimen (a mood stabilizer and an SGA) may be used for patients with a partial response to monotherapy. A third agent or ECT may be needed for patients resistant to 2-drug therapies. Clozapine is usually reserved for later stages of treatment for patients with resistant symptoms, primarily because of its side effect profile (see Table 2). For patients with depressive symptoms, lamotrigine is recommended, with or without a mood stabilizer, since it is less effective as an antimania agent.²² Therapy can be escalated in patients not responding to initial therapy to include various multidrug regimens, including combinations of mood stabilizers, SGAs, and/or antidepressants. Once efficacy with a regimen has been established for control of acute symptoms, maintenance therapy is begun, often with the same regimen that established symptom control. This regimen can then be slowly simplified to the most effective therapy that will maintain symptom remission.

Special Populations

Pregnant or breastfeeding women

A major concern regarding the treatment of BPD in pregnancy is the high rate of relapse or recurrence in the postpartum period—reported to be 32% to 67%—along with an increased risk of postpartum psychosis.¹⁵ In addition, many of the agents used for mood stabilizers are anticonvulsants, including valproic acid and carbamazepine, which are associated with adverse fetal effects. Because of the potential risks from these agents, as well as from lithium, lamotrigine has been suggested for maintenance therapy for BPD in pregnant women. With regard to the use of agents for BPD during breastfeeding, several may cross into breast milk and result in concentrations in the infant of 10% or more than maternal concentrations. The long-term effects of these agents on infant growth and neurodevelopment are unknown.¹⁷

Monitoring Parameters

As for depression, many of the agents used for the treatment of BPD are associated with significant adverse events that may interfere with patient adherence to therapy and have the potential for drug interactions due to the route of metabolism. Information on common adverse events and drug interactions with the mood stabilizers and other agents used for BPD is summarized in Table 2.

ANXIETY DISORDERS

Overview

Anxiety disorders (i.e., panic, generalized, and social anxiety) are among the most common psychiatric disorders in the United States.²³ Kessler and colleagues reported a 12-month prevalence rate for anxiety disorders of 18.1%, with a lifetime prevalence of 28.8%.^24,25 A related condition, obsessive-compulsive disorder (OCD) is less common, with 12-month and lifetime prevalence rates of 1.2% and 2.3%, respectively.²⁶ However, symptoms of OCD are more common, experienced by as much as 28% of the US adult population. Another anxiety disorder, posttraumatic stress disorder (PTSD), has a reported lifetime prevalence of about 10% in the general US population.²⁷

Anxiety disorders are generally associated with an exaggerated emotional response to a situation, either real or imagined, that is perceived to be harmful or dangerous to the individual.^28,29 Anxiety disorders are generally classified as those manifesting with either persistent anxiety (generalized), intense and unexpected episodes or attacks of anxiety (panic), or anxiety to specific situations (social).²⁸ Posttraumatic stress disorder requires a traumatic event, which the patient essentially experiences repeatedly with associated anxiety and other severe symptoms. Obsessive-compulsive disorder is associated with specific, frequent obsessive thoughts with compulsive actions done in order to alleviate the obsessive thoughts. A number of factors are thought to contribute to the development of anxiety disorders, including PTSD and OCD, such as a genetic predisposition, abnormality in brain functioning, childhood events, and stress and traumatic events occurring throughout life.^28,29 Several theories have been suggested to explain the pathophysiology of anxiety disorders. These include alterations in the neurotransmitters in the brain (e.g., norepinephrine, dopamine, and serotonin) as well as alteration in brain function and response to stimuli.^28,29 The signs and symptoms of anxiety disorders are summarized in Table 4.

Table 4. Signs and Symptoms of Anxiety Disorders^28,29
Generalized anxiety disorder	Social anxiety disorder	Panic disorder	Posttraumatic stress disorder	Obsessive compulsive disorder
Feelings of restlessness Easy fatigue Difficulty in concentrating Irritability Muscle tension Sleep disturbances	Blushing Nausea Diarrhea Sweating Tachycardia Tremors	Abdominal symptoms Chest pain Dizziness Hot flushes Palpitations Tachycardia Difficulty breathing Sweating	Anxiety Hyper-vigilance Insomnia Irritability Outbursts Difficulty concentrating	Repetitive thoughts or images Repetitive actions (hand washing, checking, counting)

The key DSM-5 criteria for the diagnosis of the various anxiety disorders are given in Table 5.⁵ Patient evaluation is an important part of the diagnosis of anxiety disorders to identify past stressful or traumatic events that may have contributed to their development or persistence.

Table 5. Key Criteria for Diagnosis of Anxiety Disorders Diagnostic and Statistical Manual of Mental Disorders-5⁵
Generalized anxiety disorder	Social anxiety disorder	Panic disorder	Posttraumatic stress disorder	Obsessive-compulsive disorder
Excessive anxiety or worry the majority of days for at least 6 months Worries are difficult to control Worry is associated with at least 3 of the symptoms listed in Table 4 Worry or anxiety causes significant impairment of functioning	Marked fear or anxiety about social situations Fear of acting in way that will be seen negatively by others Social situations are often avoided due to fear or anxiety or attended with intense fear or anxiety Fear is out of proportion with reality Fear or anxiety persists for 6 months or more Fear or anxiety causes distress or impairment of functioning	Recurrent panic attacks Presence of concern of panic attacks or a change in behavior to avoid panic attacks for at least 1 month following a panic attack	Exposure to a serious or traumatic event Presence of distressing memories or dreams, dissociative reactions, or prolonged or intense psychological distress to associated cues of the event Persistent avoidance of stimuli associated with the event Negative cognitive or mood changes associated with the traumatic event Changes in reactions associated with the traumatic event for more than a month Disturbances cause significant impact on functioning	Obsessions (unwanted recurrent and persistent thoughts) and compulsions (repetitive behaviors the individuals feels driven to perform), or both Obsessions and compulsions are time consuming

Treatment Recommendations

For all of the anxiety disorders, the goal of treatment is a reduction in symptom frequency and severity and an improvement in quality of life.^28,29

Nonpharmacologic therapy

Nonpharmacologic therapies are important aspects of treatment of anxiety disorders.^28,29Generalized anxiety, panic disorder, and social anxiety can often be treated with psychotherapy, stress management techniques, meditation, and exercise alone. For panic disorder, foods or other substances (e.g., stimulants, alcohol) that can provoke anxiety should be avoided. For social anxiety, additional therapies may consist of social skills training and self-help groups. Cognitive-behavioral approaches are considered first-line therapy for PTSD and have been shown to be effective in some patients.³⁰ Stress management and exposure-based therapies are also used.²⁹ Behavioral therapy—as exposure-response prevention—is also effective for OCD.

Pharmacologic therapy

Selective serotonin reuptake inhibitors are the main pharmacologic treatment used for anxiety disorders, including PTSD and OCD (although SNRIs are another first-line option according to some sources).³¹ An anxiolytic effect should be seen within 2 to 4 weeks of starting treatment.³² A benzodiazepine may be added on a scheduled, short-term basis for some patients if an anti-anxiety effect is needed immediately. However, their long-term use or "as needed" use is not recommended due to concerns of dependence or reliance on the agent.³¹

Response to treatment for anxiety disorders is usually considered a 25% reduction in symptom severity.³¹Patients failing to respond to initial SSRI therapy (after 6 weeks or after 12 weeks for PTSD and OCD) can be switched to another SSRI or given an SNRI.^31,32 Other classes of antidepressants may also be tried if SSRIs or SNRIs are not effective.³¹Antipsychotics (i.e., SGAs) are reserved for patients severely resistant to antidepressants. The pharmacologic agents commonly used for anxiety disorders are described in Table 2.

Monitoring Parameters

As previously mentioned, antidepressants can be associated with significant adverse events and the potential for drug interactions. This information is summarized in Table 2.

Patient Case #2

SR is a 46-year-old male who comes to your pharmacy to discuss his anxiety. He states that at times he experiences episodes of extreme anxiety along with racing heart and difficulty breathing. He is beginning to worry about leaving the house, since he does not know when this will happen again or why it happens.

Based on your knowledge of anxiety disorders, SR most likely has:

Generalized anxiety disorder
Social anxiety disorder
Panic disorder
Posttraumatic stress disorder

(Response C is correct. Panic disorder is best described as intense and unexplained episodes of extreme anxiety or panic, often accompanied by physical symptoms, such as tachycardia and shortness of breath.)

After discussing his condition with you, SR made an appointment with his physician. His physician now calls you to discuss treatment options. Which of the following would you recommend as first-line treatment for SR's anxiety disorder?

A benzodiazepine, such as diazepam, given on an as needed basis
An SSRI, such as sertraline started at 25 mg daily
An SNRI, such as duloxetine at 90 mg daily
An antipsychotic, such as aripiprazole at 5 mg daily

(Response B is correct. SSRIs are the treatment of choice for anxiety disorders in general.)

SLEEP DISORDERS

The DSM-5 describes a number of sleep disorders (referred to as sleep-wake disorders).⁵ Among these are insomnia, hypersomnolence or narcolepsy, and breathing-related sleep disorders or sleep apneas (see Table 6).

Table 6. Criteria for Diagnosis of Sleep-wake Disorders Diagnostic and Statistical Manual of Mental Disorders-5⁵
Insomnia disorder	Narcolepsy	Sleep apneas
Complaints of sleep quality/quantity (difficulty in initiating or maintaining sleep, or early morning awakenings and unable to return to sleep) Impairment of social, work, educational, or behavioral functioning Present at least 3 nights per week Present for at least 3 months Present despite adequate opportunity to sleep Not explained by other sleep-wake disorders or other physiologic conditions or substance use	Recurrent episodes of irrepressible need to sleep or falling asleep Presence of cataplexy, hypocretin deficiency, or REM sleep latency <8 to 15 minutes (depending on method of assessment)	Obstructive apnea: At least 5 obstructive apneas or hypoapneas per hour of sleep and sleep symptoms OR 15 or more obstructive apneas or hypoapneas per hour of sleep Central apnea: 5 or more central apneas per hour of sleep Not explained by another current sleep disorder
REM = rapid eye movement.

INSOMNIA AND RELATED DISORDERS

Overview

Insomnia is a common disorder, with a reported prevalence of about 22%, based on the findings of the American Insomnia Survey.³³However, symptoms of insomnia are more frequent, occurring in nearly half of the adult population.³⁴A number of chronic medical conditions, including chronic pain conditions (e.g., back pain, neuropathies, or arthritis), allergies, depression, chronic obstructive pulmonary disease, and digestive disorders (e.g., gastroesophageal reflux or irritable bowel syndrome), have been found to increase the risk of developing insomnia.³⁵Additionally, insomnia has been found to be associated with an increased risk of workplace accidents and errors, resulting in higher costs compared with accidents or errors resulting from other chronic medical conditions.³⁶

Insomnia is characterized by difficulties in falling asleep, difficulties in maintaining sleep, or too early awakenings.³⁷Causes of insomnia will vary, depending on whether insomnia is primary (idiopathic) or secondary (resulting from another underlying condition or from medications or other substances). Disturbances in sleep can result from stress or life difficulties, chronic medical conditions, or psychiatric disorders.³⁸Primary insomnia may result from neurochemical or structural abnormalities that cause an increase in metabolic rate, cortisol, or adrenocorticotropic hormone during periods of sleep. This causes a hyperarousal state resulting in insomnia or sleep disturbances.^37,39

Sleep generally cycles between nonrapid eye movement (NREM) sleep and rapid eye movement (REM) sleep.³⁹Nonrapid eye movement sleep accounts for about 75% to 80% of sleep, with the remaining being REM sleep.⁴⁰Nonrapid eye movement sleep is thought to be a time of deep rest, with decreases in blood pressure, respiratory rate, heart rate, and muscle tone. In contrast, physiologic activity during REM sleep is closer to that of wakefulness.^39,40The sleep-wake cycle is controlled by both a homeostatic process (sleep and wakefulness durations) and circadian factors.³⁹ Disturbances in either of these controlling mechanisms may disturb sleep cycles. However, the pathophysiology of insomnia is not fully known. Difficulty falling asleep, daytime fatigue or malaise, and sleepiness are common complaints of patients with insomnia.⁴⁰Patients may also have difficulty maintaining sleep throughout the night or feel unrefreshed after a full night sleep.

The DSM-5 diagnostic criteria for insomnia are listed in Table 6. Assessment of a patient's sleep-related habits are essential in making a diagnosis of insomnia.⁴⁰ These include bedtime, time to fall asleep, number of nighttime awakenings, and time of being awake. Current medication use and usual daytime activities also need to be assessed, as well as any stressful life events.

Treatment Recommendations

Goals for the treatment of insomnia are to improve sleep-wake patterns, improve daytime functioning, and identify any underlying causes contributing to insomnia.³⁴ The American Academy of Sleep Medicine (AASM) has published a clinical guideline for the management of insomnia in adults.³⁴ Per the AASM, treatment is warranted when insomnia, as a chronic condition, significantly interferes with an individual's daily function as well as quality of sleep.

Nonpharmacologic therapy

Nonpharmacologic or behavioral therapies are the main treatment approaches for both primary and secondary insomnia.³⁴ These include sleep hygiene, relaxation, stimulus control, and sleep restriction (see Table 7).⁴¹ Nonpharmacologic therapies have been shown to be successful in 25% to 50% of patients.

Table 7. Nonpharmacologic Therapies for Insomnia^34,41
Sleep hygiene	Relaxation	Stimulus control	Sleep restriction
Regular sleep/wake schedules Avoid caffeinated beverages starting in the afternoon Avoid alcohol or smoking in the evening or near bedtime Regular exercise 4 to 5 hours prior to bedtime Sleep only long enough to feel rested	Progressive muscle relaxation Biofeedback Guided imagery Abdominal breathing	Go to bed only when sleepy Get out of bed if not able to fall asleep within 20 minutes No television, reading, eating, or staying awake while in bed Wake at the same time each day Avoid naps	Limits time in bed to "total sleep time" as determined by sleep diaries Time in bed for sleep is gradually increased

Pharmacologic therapy

A large number of pharmacologic agents have been used for the treatment of insomnia, including benzodiazepine receptor agonists (BzRAs, both benzodiazepine and nonbenzodiazepines), melatonin receptor agonists, antidepressants, anticonvulsants, and antihistamines.³⁴

The AASM clinical guideline recommends a short- or intermediate-acting BzRA (e.g., zaleplon, zolpidem, eszopiclone, estazolam, triazolam, or temazepam) or ramelteon (a melatonin receptor agonist) as the initial pharmacologic treatment for insomnia (Table 8).³⁴ No preference is given to one of these agents over another, with the exception of triazolam. Because of the associated rebound anxiety, it is not recommended as a first-line agent. Selection depends on the disturbance in sleep patterns that the patient is experiencing: difficulty falling asleep versus difficulty maintaining sleep. Patients not responding to initial therapy may be given an alterative agent from this group. A low dose of a sedating antidepressant agent (e.g., doxepin, amitriptyline, trazodone, mirtazapine) may be tried for treatment failures, although efficacy of these agents may be low. Other medications, such as antipsychotics or anticonvulsants, are generally not recommended because of the risk of side effects and limited efficacy data.

Table 8. Agents for Treatment of Insomnia^34,37,41-43*
Agent (dosage forms)	Adult initial dose at bedtime	Primary use/duration
Benzodiazepine receptor agonistic modulators
Benzodiazepines
Estazolam (1, 2 mg tablets)	1 to 2 mg; 0.5 to 1 mg for elderly or debilitated patients	Sleep-onset and maintenance Short- to intermediate-acting
Temazepam (7.5, 15, 22.5, 30 mg capsules)	15 to 30 mg; 7.5 to 15 mg for elderly or debilitated patients	Sleep-onset and maintenance Short- to intermediate-acting
Triazolam (0.125, 0.25 mg tablets)	0.25 to 0.5 mg 0.125 mg for elderly or debilitated patients	Sleep-onset Short-acting
Nonbenzodiazepines
Eszopiclone (1, 2, 3 mg tablets)	1 mg; may be increased to 2 or 3 mg if needed Total dose should not exceed 2 mg in elderly or debilitated patients	Sleep-onset and maintenance Intermediate-acting
Zolpidem (5, 10 mg tablets;1.75, 3.5, 5, 10 mg sublingual tablets; 5 mg/spray oral spray)	5 to 10 mg as oral or sublingual tablets and spray mist; 5 mg for women, elderly, or debilitated patients or for those with hepatic impairment 3.5 mg as sublingual tablets to be taken upon middle of the night awakening; 1.75 mg for women, elderly, or with hepatic impairment	Sleep-onset and maintenance Short- to intermediate-acting
Zolpidem CR (6.25, 12.5 mg controlled-release tablets)	6.25 to 12.5 mg; 6.25 mg for women, elderly, or debilitated patients or for those with hepatic impairment	Sleep-onset and maintenance Controlled-release
Zaleplon (5, 10 mg capsules)	10 to 20 mg; 5 mg for elderly or debilitated patients, with hepatic impairment, or on concurrent cimetidine	Sleep-onset Short-acting
Melatonin-receptor agonists
Ramelteon (8 mg tablets)	8 mg	Sleep-onset Short-acting
*Dosage may vary dependent upon reference source.

Monitoring Parameters

A 2- to 4-week course of treatment can be used initially, to determine efficacy as well as the need for continued treatment.³⁴ There are few recommendations on long-term therapy, but if used, patients should be evaluated often, every 6 months, to determine need, tolerance, and risk of abuse. Once treatment is no longer needed, medications should be slowly tapered to avoid rebound insomnia or withdrawal symptoms.

NARCOLEPSY

Overview

Narcolepsy is a rare disorder, with a reported prevalence of 1 in 2000 individuals in the United States.^37,41 Over half of the patients with narcolepsy also experience a sudden and short-lived loss of muscle tone, referred to as narcolepsy with cataplexy.³⁹ Factors contributing to narcolepsy include genetics, with a 10- to 40-fold higher prevalence in patients with affected family members compared to the general population, along with an environmental influence. Autoimmune effects may also contribute.⁴¹ The pathophysiology of narcolepsy is not fully known, but may be related to a reduction in orexin (hypocretin), a neuropeptide secreted during waking hours.^39,41 A depletion of this neuropeptide, either via an autoimmune disorder or degeneration of the cells necessary for its production, is suggested as a possible pathophysiology of narcolepsy. Patients with narcolepsy experience excessive daytime sleepiness with often irresistible sleep attacks.³⁷ Vivid hallucinations may be present when falling asleep or waking up.

The DSM-5 diagnostic criteria for narcolepsy are listed in Table 6.⁵ The most common age of onset is late adolescence or young adulthood.³⁷ Polysomnography and the multiple sleep latency tests are often used to confirm the diagnosis.

Treatment Recommendations

The goal of therapy is alleviation of daytime sleepiness and return of normal daily functioning for the individual with narcolepsy.⁴³

Nonpharmacologic therapy

Nonpharmacologic therapy for narcolepsy consists of short daytime naps to alleviate sleepiness, regular bedtimes, keeping meals small, and avoiding alcohol.³⁹ However, these interventions have limited effectiveness for most individuals.

Pharmacologic therapy

Several agents are available for treatment of narcolepsy.⁴⁴ Stimulants are the most frequently used pharmacotherapy, including modafinil, amphetamines, and methylphenidate. For modafinil, doses of 200 to 600 mg daily (as a split dose) have been effective in relieving daytime sleepiness in patients with narcolepsy. Amphetamines and other stimulants are also effective, but there are limited data on their risk to benefit ratio. Sodium oxybate is a newer agent approved for use in the treatment of narcolepsy and related disorders.¹²It is dosed at bedtime, with a repeat dose 2.5 to 4 hours later. Because of the potential for abuse and adverse effects, sodium oxybate is only available via a restricted access program.

Monitoring Parameters

Of the available agents for treatment of narcolepsy, sodium oxybate may be associated with the most serious side effects, including central nervous system (CNS) depression, respiratory depression, coma, seizure, a risk of depression or suicidality, along with a risk of abuse.¹² Dosing of sodium oxybate is also problematic, since a second dose is needed a few hours after bedtime. Alcohol and CNS depressants need to be avoided with sodium oxybate.

SLEEP APNEA

Overview

Sleep apneas are a common sleep disorder, affecting millions of individuals in the United States.³⁸ Sleep apneas can be classified as obstructive or central. Obstructive sleep apnea (OSA), the more common of the 2 disorders, results from a collapse of the upper airway but with a normal respiratory drive.⁴⁵ In contrast, central sleep apnea (CSA) is associated with a reduced respiratory drive. Both conditions cause apnea, a cessation of airflow for 10 or more seconds, along with daytime sleepiness and nighttime awakenings.^45,46

Obstructive sleep apnea results from both anatomical and neurological factors.^41,45,47During sleep, upper airway patency is maintained by various upper respiratory muscles that oppose forces that promote airway collapse, such as the negative pressure of ventilation. With a loss of upper airway neuromuscular tone, the balance between forces that maintain airway patency and those that promote airway collapse is lost, resulting in upper airway closure and cessation of breathing. In contrast, CSA results from alterations in the ventilatory drive during sleep, either hypoventilation or hyperventilation, due to dysfunction of neuromuscular ventilatory control.⁴⁶ Both obstructive and central sleep apneas manifest with apnea during periods of sleep.⁴⁷ For OSA, episodes of hypoapnea may also occur, which is defined as a reduction in airflow (30% to 50% or more) for at least 10 seconds. Patients with sleep apneas often experience daytime sleepiness, restless sleep, fatigue, and a decrease in cognition.

The DSM-5 diagnostic criteria for sleep apneas are listed in Table 6.⁵ Sleep testing using polysomnography can help distinguish between obstructive and central sleep apneas.⁴¹

Treatment Recommendations

Untreated, sleep apneas can result in significant morbidity and increased mortality, as well as reduced quality of life, making appropriate treatment essential. Therapy for sleep apneas also includes identification and treatment of any contributing underlying medical conditions.

Treatment of sleep apneas, both OSA and CSA, is primarily nonpharmacologic. For OSA, treatment strategies include positive airway pressure devices (continuous, bilevel, or autotitrating devices), oral appliances (e.g., for mandibular repositioning), and surgery.⁴⁸ For most patients with CSA, continuous positive airway pressure is the preferred treatment of choice.⁴⁶ Supplemental oxygen may also benefit some patients. Pharmacologic therapy (e.g., zolpidem, triazolam, acetazolamide, and theophylline) has been used; however, data are limited, and these agents are considered options only when nonpharmacologic therapies have not been effective.

EATING DISORDERS

Overview

For all eating disorders, the lifetime prevalence has been reported to be about 5%.⁴⁹ The rate is higher when only adolescents are considered, up to 13% among girls. However, a true assessment of the prevalence of eating disorders is difficult, since many patients do not seek medical care.⁵⁰Eating disorders have been broadly classified as anorexia nervosa, bulimia nervosa, and eating disorders–not otherwise specified.^49,51 In all 3 classifications, patients are preoccupied with body image, both body weight and body shape. There are a multitude of factors that may contribute to the development of an eating disorder, including genetic, biologic, sociocultural, and familial factors.^49,52

The pathophysiology of eating disorders has not been fully explained. However, imaging studies have revealed changes in brain mass in patients with eating disorders.⁵²Dysfunction of various neurotransmitters, such as dopamine and serotonin, or their transport may also be involved. Patients with eating disorders present with distorted self-image of body size and shape, along with behaviors to promote weight loss or prevent weight gain.⁵³ These can include severe restriction of calories along with excessive exercise or purging (vomiting or laxative use). With anorexia nervosa, calorie intake is inadequate to maintain a healthy weight. For bulimia nervosa, calorie intake is in the normal to high range, with cycles of dieting and overeating (as binge-purge episodes). The DSM-5 criteria for the diagnosis of eating disorders are given in Table 9.⁵

Table 9. Criteria for Diagnosis of Anorexia Nervosa and Bulimia Nervosa Diagnostic and Statistical Manual of Mental Disorders-5⁵
Anorexia nervosa	Bulimia nervosa
Calorie restriction to less than required; significantly low body weight for age and development Intense fear of weight gain with behavior to prevent (needed) weight gain Distorted view of body weight or shape and its influence on self-image, or failure to recognize seriousness of low body weight Level of severity (as BMI): Mild: ≥17 kg/m² Moderate: 16 to 16.99 kg/m² Severe: 15 to 15.99 kg/m² Extreme: <15 kg/m²	Recurrent episodes of binge eating Recurrent behavior or activities to prevent weight gain (vomiting, laxative or diuretic use, fasting, or excessive exercise) Binge eating and weight gain prevention occur at least once a week for 3 months Body weight and shape inappropriately influence self-evaluation Behavior not part of episodes of anorexia nervosa Level of severity (as episodes/week):
BMI = body mass index.

Treatment Recommendations

Once diagnosed, part of the therapeutic goal for eating disorders is patient acceptance that an eating disorder is present.⁵³ In addition to achieving normal eating patterns and an appropriate weight, treatment of eating disorders also needs to address any comorbid conditions—medical or psychiatric—as well as reduce the risk of mortality.^49,51 Since eating disorders are more common among adolescents (although the disorder may continue into adulthood), the AAP has outlined treatment recommendations for eating disorders.⁵⁴

Nonpharmacologic therapy

Most treatment approaches for eating disorders are nonpharmacologic, using a multidisciplinary approach consisting of medical, nutritional, social, and psychological support.⁴⁹ Treatment can be conducted on an outpatient basis but for severe cases, hospitalization may be needed. Behavioral interventions and nutritional rehabilitation are necessary, along with family-based therapy.⁵⁴

Pharmacologic therapy

Pharmacologic therapy has also been used for eating disorders, with stronger evidence available for bulimia nervosa than for anorexia nervosa.^49,54Various agents have been used, including antidepressants, antipsychotics, and anticonvulsants for both anorexia nervosa and bulimia nervosa.⁴⁹ Olanzapine, an SGA, has been reported to result in weight gain and improvement in dysfunctional thinking among patients with anorexia nervosa, although the effects have been described as modest.⁵⁴ Selective serotonin reuptake inhibitor antidepressants appear to have the strongest evidence for use in eating disorders, but mainly for bulimia nervosa and only for short-term use during initial treatment. The beneficial effects of SSRIs have been described as slight. Of note, lisdexamfetamine became the first FDA-approved treatment of moderate to severe binge eating disorder in January 2015.⁵⁵ Treatment with lisdexamfetamine resulted in a reduction in the number of binge eating days/week and fewer obsessive-compulsive binge eating behaviors compared to placebo.

Monitoring Parameters

Pharmacologic therapy is not a first-line treatment for eating disorders, so monitoring for drug interactions or adverse events is limited. However, these patients may have multiple comorbid conditions where drug therapy is warranted. Because of poor nutrition and extremely low body weights (especially for anorexia nervosa), medical complications such as osteoporosis or osteopenia, esophagitis (due to repeated vomiting), anemias, and electrolyte abnormalities may be present and require treatment.⁵

SCHIZOPHRENIA

Overview

Various prevalence rates have been reported for schizophrenia and generally range from 2.7 to 8.3 per 1000 individuals.⁵⁶ Men are affected more often than women (with about a 30% to 40% higher lifetime risk) and usually exhibit symptoms about 3 to 4 years earlier than women.⁵⁷ The peak onset of schizophrenia is late adolescence or early adulthood (usually 15 to 24 years of age).⁵⁶ Both genetic and environmental factors have been implicated in the development of schizophrenia, with a possible greater contribution by environmental factors (e.g., head injury, substance abuse, place and season of birth, and prenatal infections or obstetric complications).⁵⁷

Abnormalities in both brain structure and function have been suggested as possible causes for schizophrenia.⁵⁷ Dopamine has been the neurotransmitter thought to be involved in the pathophysiology of schizophrenia, with a focus on the dopamine-2 receptor subtype. Other neurotransmitters and receptors are also being investigated for a possible role in the disorder.⁵⁸ Symptoms of schizophrenia can appear acutely or, more commonly, following a period of behavioral changes including increased suspicion, social withdrawal, obsessive thoughts, and distorted thinking.^57,59 Acute psychosis manifests with hallucinations, delusions, and thoughts of external control of one's actions. Depression and suicidality are also often present. Symptoms are classified as positive (hallucinations, delusions, unusual behavior), negative (loss of interest or drive, ambivalence), and cognitive (poor attention, impaired memory, disorder of thought).⁵⁸

The DSM-5 provides specific criteria for the diagnosis of schizophrenia.⁵ These include the presence of delusions, hallucinations, disorganized speech, disorganized or catatonic behavior, or negative symptoms. One of these symptoms must be present for 1 month along with a decrease in the level of work/social functioning or self-care; continuous signs for at least 6 months; lack of an underlying physiologic cause or drug effect; or no other psychiatric illness that may cause the symptoms (including MDD and BPD). The Positive and Negative Syndrome Scale (PANSS) is commonly used to determine severity of symptoms present; the Brief Psychiatric Rating Scale (BPRS) is used to assess response to treatment.⁶⁰

Treatment Recommendations

Schizophrenia is a chronic disorder that is associated with a shortened life expectancy, due to suicide and an increase in cardiovascular and metabolic diseases.⁵⁷ Therefore, achieving and maintaining remission of the symptoms of schizophrenia to allow for more normal functioning is the goal of treatment. Treatment recommendations for schizophrenia have been provided by several organizations, including the APA, the Texas Medication Algorithm Project (TMAP), and the Schizophrenia Patient Outcomes Research Team (PORT).^61-64

Nonpharmacologic therapy

For patients with schizophrenia, nonpharmacologic therapies focus on social services, including community support, employment assistance, and skill training; cognitive behavioral therapy; and family-based services.⁶⁵ These therapies, along with pharmacologic treatments, can improve quality of life for patients with schizophrenia and their families and reduce the risk of homelessness and hospitalizations.

Pharmacologic therapy

Antipsychotic medications are first-line treatment for patients experiencing acute episodes of schizophrenia (see Table 2).^62,63 For a first-episode of schizophrenia, the TMAP recommends an SGA for example, aripiprazole, olanzapine, quetiapine, risperidone, or ziprasidone.⁶² Clozapine and first-generation antipsychotics (FGAs; e.g., phenothiazines) are usually held for later therapy in patients not responding to SGAs; clozapine can be considered for early treatment among patients at risk for suicide or who are violent. Recommendations from PORT are similar, (including holding clozapine for patients with resistant symptoms) with the exception of recommending FGAs as a first-line option.⁶³ Studies cited in the PORT recommendations indicate no difference in short-term efficacy between FGAs and SGAs. However, SGAs may have long-term advantages over FGAs in regards to remission rates and treatment adherence. Regardless of which antipsychotic is used, for a first episode of schizophrenia, the lowest effective dose should be used and consideration given to the side effect profile of the individual antipsychotics.⁶⁴ Once acute symptoms have resolved, antipsychotics should be continued as maintenance therapy to prevent relapse of acute symptoms.⁶³ Long-acting injectable antipsychotics may be used in place of oral therapy if adherence to oral therapy is of concern. For exacerbations of symptoms, antipsychotics are again the first-line of treatment, using either an antipsychotic that had been effective in the past for acute episodes or a new antipsychotic.

Special Populations

Pregnant or breastfeeding women

If untreated, schizophrenia can have significant detrimental effects during pregnancy, including failure to seek prenatal care and potential harm to the infant.¹⁶ Therefore, continued treatment with antipsychotics is essential in most cases.⁶⁶ The effects of antipsychotics on the fetus are not fully known, so the lowest effective dose of any antipsychotic should be used.¹⁶ Information is also limited in regards to the use of antipsychotics during breastfeeding.¹⁸

Monitoring Parameters

Antipsychotics used for treatment of schizophrenia are associated with significant adverse events that can interfere with patients' adherence. Similarly, the potential for drug interactions may be high for some agents due to their metabolic route. Information on adverse events and drug interactions for antipsychotics is summarized in Table 2.

SUBSTANCE ABUSE

Overview

Information on the epidemiology of substance abuse in the United States is available from the National Survey on Drug Use and Health, conducted by the US Department of Health and Human Services, Substance Abuse and Mental Health Services Administration (SAMHSA).⁶⁷ For the year 2014, it was reported that 10.2% of the US population over the age of 12 years had used some type of illicit drug during the time surveyed. These illicit drugs included marijuana, cocaine, heroin, hallucinogens, inhalants, or prescription drugs (e.g., stimulants, tranquilizers, or sedatives). This number represents an increase in illicit drug use, up from 8.1% in 2008. Marijuana was the most commonly used substance of abuse, followed by prescription pain relievers. The various types of substances of abuse and their common clinical effects are listed in Table 10.

Table 10. Common Substances of Abuse^68-72
Classification	Included substances	Acute clinical effects
CNS depressants	Opiates/opioids	Euphoria, altered levels of consciousness, respiratory depression
	Benzodiazepines	Slurred speech, poor coordination, memory impairment, drowsiness
	Carisoprodol	Drowsiness, dizziness, headache, agitation, ataxia, tremor, irritability
	Dextromethorphan	Hyperexcitability, lethargy, ataxia, slurred speech, diaphoresis, hypertension
CNS stimulants	Cocaine	Headache, hyperventilation, dyspnea, chest pain, wheezing, tremor, psychosis, seizures
	Amphetamines, methamphetamines	Tachycardia, hypertension, increased physical activity, euphoria, decreased appetite, increased wakefulness
	Synthetic cathinones (bath salts)	Agitation, confusion, hallucinations, tremor, fever, chest pain, palpitations, hypertension, tachycardia, seizures, acute renal failure
Hallucinogens	Lysergic acid diethylamide (LSD)	Diaphoresis, tachycardia, hypertension, nausea, seizures, tremor
	Phencyclidine (PCP)
	MDMA ("Ecstasy")
Inhalants	Hydrocarbon-based substances (e.g., petroleum distillates, acetone, trichloroethylene, chlorofluorocarbons, xylene, esters, trichloroethane)	Dizziness, incoordination, slurred speech, lethargy, muscle weakness, slow thinking and movement, chemical burns, ventricular arrhythmias
	Glues
	Spray paints
	Hair spray
	Dry cleaning agents
	Spot removers
	Nail polish remover
	Paint thinner
	Anesthetics (nitrous oxide, halothane, isoflurane, ethyl chloride)
Cannabinoids	Marijuana	Sudden hunger, thirst, feelings of paranoia and anxiety, headache, tremor, ataxia, tachycardia
Cannabinoids	Synthetic cannabinoids (e.g., Spice, K2, Aroma)	Anxiety, tachycardia, psychosis, agitation, paranoia, cognitive impairment
CNS = central nervous system; MDMA = 3,4-methylenedioxy-N-methylamphetamine.

Treatment Recommendations

Treatment of substance abuse varies widely and depends largely on the substance ingested.

Acute intoxication

For acute intoxication, therapy is primarily supportive, ensuring adequate respiratory function and prevention of complications.⁷¹However, pharmacologic treatment is sometimes necessary. For example, severe agitation from hallucinogens or inhalants may require use of a benzodiazepine, such as lorazepam, or an antipsychotic, such as haloperidol, to control symptoms acutely.^68,71 Naloxone may be needed to reverse the respiratory depressant effects of opioids. Flumazenil is available to reverse the sedative effects of benzodiazepines.¹²

Withdrawal

Severity of withdrawal symptoms following discontinuation of the use of the substance will depend on the duration of substance abuse. Withdrawal symptoms are usually the opposite of the clinical effects caused by the substance of abuse.⁷¹ In some cases, tapering the dose of the abused agent or substituting a long-acting equivalent may prevent or alleviate symptoms of withdrawal. Clonidine, methadone, and buprenorphine have been used for withdrawal from opioids with the dose tapered over a set period of time.⁶⁸ For benzodiazepines and other sedative-hypnotics, the dose of the agent has been reduced by 10% or less every 1 to 2 weeks until a 75% dose reduction is reached, and then by 5% every 2 to 4 weeks.⁷¹

Dependence

Following treatment of withdrawal, longer-term therapies may be needed to prevent patients from reverting to substance abuse. Cognitive behavioral therapy, 12-step programs, and other psychosocial approaches are generally first-line for substance abuse recovery.^70,71 For individuals with opioid dependence, methadone, clonidine, naltrexone, and buprenorphine/naloxone have been used for long-term management.

Monitoring Parameters

Pharmacologic therapy is generally a supportive measure used early in the treatment of substance abuse to alleviate symptoms of withdrawal and at times long-term to prevent relapse to substance abuse.⁶⁸ Medication guides are required with buprenorphine-containing products, including buprenorphine/naloxone, and for methadone as part of their Food and Drug Administration's Risk Evaluation and Mitigation Strategies (REMS) programs.¹² Methadone also carries a box warning regarding the risk for respiratory depression, abuse potential, QT prolongation, and requirements for its use in opioid detoxification/maintenance programs.

Focus Points For Medication Therapy Management (MTM) in Psychiatric Disorders

Patient education

Discuss with patients realistic goals and expectations from medication therapy
The goal of treatment is to relieve acute symptoms, prevent recurrence, and improve overall quality of life
Some medications, such as for MDD and anxiety disorders, do not exert their full effect for several weeks
Reinforce to patients that symptoms may resolve or remit slowly, but improvement should be noticed within a few weeks, with full effects not seen for up to 8 weeks, depending on the medication used
In some cases, some type of psychological therapy (cognitive-behavioral therapy, family-based therapy) will help in improving symptoms and also prevent recurrence
Adherence to medication is critical for psychiatric disorders, especially in disorders such as schizophrenia where long-term maintenance therapy is often needed
Patients need to be counseled to continue medication as prescribed
- Abrupt discontinuation may result in a sudden worsening of symptoms or in withdrawal symptoms
- Adverse events are common with many of the medications used to treat psychiatric disorders. Many are mild and often resolve with continued therapy

Medication therapy management

Drug interactions are common with many of the medications used for psychiatric disorders

References

Centers for Disease Control and Prevention. Mental illness surveillance among adults in the United States. MMWR Morb Mortal Wkly Rep. 2011;60(Suppl):1-11.
Hasin DS, Goodwin RD, Stinson FS, Grant B. Epidemiology of major depressive disorder. Arch Gen Psychiatry. 2005;62(10):1097-1106.
Kessler RC, Berglund P, Demler O, et al. The epidemiology of major depressive disorder. Results from the National Comorbidity Survey Replication (NCS-R). JAMA. 2003;289(23):3095-3105.
Saveanu RV, Nemeroff CB. Etiology of depression: genetics and environmental factors. Psychiatr Clin N Am. 2012;35(1):51-71.
American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 5th ed. Arlington, VA: American Psychiatric Publishing; 2013.
Schneiderhan ME, Nelson L, Dellenbaugh T. Evaluation of psychiatric disorders. In: DiPiro JT, Talbert RL, Yee GC, et al, eds. Pharmacotherapy: A Pathophysiologic Approach. 9th ed. New York, NY: McGraw-Hill; 2014. http://accesspharmacy.mhmedical.com/content.aspx?sectionid=48811445&bookid=689&jumpsectionID=48834354&Resultclick=2. Accessed May 1, 2016.
Soleimani L, Lapidus KAB, Iosifescu DV. Diagnosis and treatment of major depressive disorder. Neurol Clin. 2011;29(1):177-193.
American Psychiatric Association. Practice guideline for the assessment and treatment of patients with suicidal behaviors. 2003. http://psychiatryonline.org/pb/assets/raw/sitewide/practice_guidelines/guidelines/suicide.pdf. Accessed May 2, 2016.
American Psychiatric Association. Practice guideline for the treatment of patients with major depressive disorder. 3rd ed, 2010. https://psychiatryonline.org/pb/assets/raw/sitewide/practice_guidelines/guidelines/mdd.pdf. Accessed May 2, 2016.
Teter CJ, Kando JC, Wells BG. Major depressive disorder. In: DiPiro JT, Talbert RL, Yee GC, Matzke GR, et al, eds. Pharmacotherapy: A Pathophysiologic Approach, 9th ed. New York, NY: McGraw-Hill; 2014. http://accesspharmacy.mhmedical.com/content.aspx?sectionid=45310502&bookid=689&Resultclick=2. Accessed May 2, 2016.
Mann JJ. The medical management of depression. N Engl J Med. 2005;353(17):1819-1834.
Wickersham RM, ed. Drug Facts and Comparisons. St. Louis, MO: Wolters Kluwer Health; 2016. http://online.factsandcomparisons.com. Accessed May 2, 2016.
Anon. Drugs for psychiatric disorders. Treat Guidel Med Lett. 2013;11(130):53-64.
Chaudron LH. Complex challenges in treating depression during pregnancy. Am J Psychiatry. 2013;170(1):12-20.
ACOG Committee on Practice Bulletins—Obstetrics. ACOG Practice Bulletin: Clinical management guidelines for obstetrician-gynecologists number 92, April 2008 (replaces practice bulletin number 87, November 2007). Use of psychiatric medications during pregnancy and lactation. Obstet Gynecol. 2008;111(4):1001-1020.
Yonkers KA, Wisner KL, Stewart DE, et al. The management of depression during pregnancy: a report from the American Psychiatric Association and the American College of Obstetricians and Gynecologists. Gen Hosp Psychiatry. 2009;31(5):403-413.
Sachs HC, The Committee on Drugs. The transfer of drugs and therapeutics into human breast milk: an update on selected topics. Pediatrics. 2013;132(3):e796-e809.
Perlis RH, Ostacher MJ. Bipolar disorder. In: Stern TA, Fava M, Wilens TE, Rosenbaum JF, eds. Stern: Massachusetts General Hospital Comprehensive Clinical Psychiatry. 2nd ed. Philadelphia, PA: Mosby Elsevier; 2016:330-342.
Khalife S, Singh V, Muzina DJ. Bipolar disorder. In: Carey WD, ed. Cleveland Clinic: Current Clinical Medicine. 2nd ed. Cleveland, OH: The Cleveland Clinic; 2010:966-971.
Drayton SJ, Pelic CM. Bipolar disorder. In: DiPiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey L. eds. Pharmacotherapy: A Pathophysiologic Approach, 9th ed.New York, NY: McGraw-Hill; 2014. http://accesspharmacy.mhmedical.com/content.aspx?sectionid=45310503&bookid=689&Resultclick=2. Accessed May 2, 2016.
American Psychiatric Association. Practice guideline for the treatment of patients with bipolar disorder. 2nd ed, 2002. http://psychiatryonline.org/pb/assets/raw/sitewide/practice_guidelines/guidelines/bipolar.pdf. Accessed May 2, 2016.
Suppes T, Dennehy EB, Hirschfeld RM, et al. The Texas implementation of medication algorithms: update to the algorithms for treatment of bipolar I disorder. J Clin Psychiatry. 2005; 66(7):870-886.
Calkins AW, Bui E, Taylor CT, Pollack MH, LeBeau RT, Simon NM.. Anxiety disorders.. In: Stern TA, Fava M, Wilens TE, Rosenbaum JF, eds. Stern: Massachusetts General Hospital Comprehensive Clinical Psychiatry. 2nd ed. Philadelphia, PA: Mosby Elsevier; 2016:353-366.
Kessler RC, Chiu WT, Demler O, et al. Prevalence, severity, and comorbidity of 12-month DSM-IV disorders in the National Comorbidity Survey Replication. Arch Gen Psychiatry. 2005;62(6):617-627.
Kessler RC, Berglund P, Demler O, et al. Lifetime prevalence and age-of-onset distributions of DSM-IV disorders in the National Comorbidity Survey Replication. Arch Gen Psychiatry. 2005;62(6): 2005;62(6):593-602.
Ruscio AM, Stein DJ, Chiu WT, Kessler RC. The epidemiology of obsessive-compulsive disorder in the National Comorbidity Survey Replication. Mol Psychiatry. 2010;15(1):53-63.
Shalev AY. Posttraumatic stress disorder and stress-related disorders. Psychiatr Clin N Am. 2009;32(3):687-704.
Melton ST, Kirkwood CK. Anxiety disorders I: Generalized anxiety, panic, and social anxiety disorders. In: DiPiro JT, Talbert RL, Yee GC, et al. Pharmacotherapy: A Pathophysiologic Approach, 9th ed. New York, NY: McGraw-Hill; 2014. http://accesspharmacy.mhmedical.com/content.aspx?sectionid=45310504&bookid=689&Resultclick=2. Accessed May 3, 2016.
Kirkwood CK, Melton ST, Wells BG. Anxiety disorders II: Posttraumatic stress disorder and obsessive-compulsive disorder. In: DiPiro JT, Talbert RL, Yee GC, et al, eds. Pharmacotherapy: A Pathophysiologic Approach, 9th ed.New York, NY: McGraw-Hill; 2014. http://accesspharmacy.mhmedical.com/content.aspx?sectionid=45310505&bookid=689&Resultclick=2. Accessed May 3, 2016.
Dekel S, Gilbertson MW, Orr SP, Rauch SL, Wood NE, Pitman RK. Trauma and posttraumatic stress disorder. In: Stern TA, Fava M, Wilens TE, Rosenbaum JF, eds. Stern: Massachusetts General Hospital Comprehensive Clinical Psychiatry. 2nd ed. Philadelphia, PA: Mosby Elsevier; 2016:380-394.
Farach FJ, Pruitt LD, Jun JJ, et al. Pharmacological treatment of anxiety disorders: current treatment and future directions. J Anxiety Disord. 2012;26(8):833-843.
Bandelow B, Sher L, Bunevicius R, et al. Guidelines for the pharmacological treatment of anxiety disorders, obsessive-compulsive disorder and posttraumatic stress disorder in primary care. Int J Psychiatry Clin Pract. 2012;16(2):77-84.
Roth T, Coulouvrat C, Hajak G, et al. Prevalence and perceived health associated with insomnia based on DSM-IV-TR; International Statistical Classification of Diseases and Related Health Problems, Tenth Revision; and Research Diagnostic Criteria/International Classification of Sleep Disorders, Second Edition criteria: results from the America Insomnia Survey. Biol Psychiatry. 2011;69(6):592-600.
Schutte-Rodin S, Broch L, Buysse D, et al. Clinical guideline for the evaluation and management of chronic insomnia in adults. J Clin Sleep Med. 2008;4(5):487-504.
Kessler RC, Berglund PA, Coulouvrat C, et al. Insomnia, comorbidity, and risk of injury among insured Americans: results from the American Insomnia Survey. Sleep. 2012;35(6):825-834.
Shahly V, Berglund PA, Coulouvrat C, et al. The association of insomnia with costly workplace accidents and errors. Arch Gen Psychiatry. 2010;69(10):1054-1063.
Buysse DJ. Insomnia. JAMA. 2013;309(7):706-716.
Dopp JM, Phillips BG. Sleep disorders. In: DiPiro JT, Talbert RL, Yee GC, et al, eds. Pharmacotherapy: A Pathophysiologic Approach, 9th ed.New York, NY: McGraw-Hill; 2014. http://accesspharmacy.mhmedical.com/content.aspx?sectionid=45310506&bookid=689&Resultclick=2. Accessed May 3, 2016.
Weilburg JB, Stakes JW, Bianchi M, Gerstenblith TA. Sleep disorders. In: Stern TA, Fava M, Wilens TE, Rosenbaum JF, eds. Stern: Massachusetts General Hospital Comprehensive Clinical Psychiatry. 2nd ed. Philadelphia, PA: Mosby Elsevier; 2016:229-246.
Lim LL, Foldvary-Schaefer N. Sleep disorders. In: Carey WD, ed. Cleveland Clinic: Current Clinical Medicine. 2nd ed. Cleveland, OH: The Cleveland Clinic; 2010:914-921.
Chokroverty S, Avidan AY. Sleep and its disorders. In: Daroff RB, Jankovic J, Mazziotta JC, Pomeroy SL eds. Daroff: Bradley's Neurology in Clinical Practice. 7th ed. Philadelphia, PA: Elsevier Saunders; 2016:1615-1685.
Anon. Drugs for insomnia. Treat Guidel Med Lett. 2012;10(119):57-60.
Lunesta [package insert]. Marlborough, MA: Sunovion Pharmaceuticals; 2014.
Morgenthaler TI, Kapur VK, Brown TM, et al. Practice parameters for the treatment of narcolepsy and other hypersomnias of central origin. Sleep. 2007;30(12):1705-1711.
Yaggi KH, Strohl KP. Adult obstructive sleep apnea/hypoapnea syndrome: definitions, risk factors, and pathogenesis. Clin Chest Med. 2010;31(2):179-186.
Aurora RN, Chowdhuri S, Ramar K, et al. The treatment of central sleep apnea syndromes in adults: practice parameters with an evidence-based literature review and meta-analysis. Sleep. 2012;35(1):17-40.
Wakefield TL, Lam DJ, Ishman SL. Sleep apnea and sleep disorders. In: Flint PW, Haughey BR, Lund V, et al, eds. Flint: Cummings Otolaryngology: Head & Neck Surgery. 6th ed. Philadelphia, PA: Mosby Elsevier; 2015:252-270.
Adults Obstructive Sleep Apnea Task Force of the American Academy of Sleep Medicine. Clinical guideline for the evaluation, management and long-term care of obstructive sleep apnea in adults. J Clin Sleep Med. 2009;5(3):263-276.
Treasure J, Claudino A, Zucker N. Eating disorders. Lancet. 2010;375(9714):583-593.
Hoek HW. Incidence, prevalence and mortality of anorexia nervosa and other eating disorders. Curr Opin Psychiatry. 2006;19(4):389-394.
Herpertz-Dahlmann B. Adolescent eating disorders: definitions, symptomatology, epidemiology and comorbidity. Child Adolesc Psychiatric Clin N Am. 2008;18(1):31-47.
Herpertz-Dahlmann B, Holtkamp K, Konrad K. Eating disorders: anorexia and bulimia nervosa. Handbook of Clinical Neurology. 2012;106(26):447-462
Kreipe RE. Eating disorders. In: Kliegman: Nelson Textbook of Pediatrics. Kliegman RM, Stanton BF, St. Geme JW, Schor NF, eds. 20th ed. Philadelphia, PA: Elsevier Saunders: 2016;162-170.
Rosen DS; American Academy of Pediatrics Committee on Adolescence. Identification and management of eating disorders in children and adolescents. Pediatrics. 2010;126(6):1240-1253.
Vyvanse [package insert]. Lexington, MA: Shire US Inc.; 2015.
Messias ER, Chen C, Eaton WW. Epidemiology of schizophrenia: review of findings and myths. Psychiatr Clin N Am. 2007;30(3):323-338.
Freudenreich O, Brown HE, Holt DJ. Psychosis and schizophrenia. In: Stern TA, Fava M, Wilens TE, Rosenbaum JF, eds. Stern: Massachusetts General Hospital Comprehensive Clinical Psychiatry. 2nd ed. Philadelphia, PA: Mosby Elsevier; 2016:307-323.
Mathews M, Tesar GE, Fattal O, et al. Schizophrenia and acute psychosis. In: Carey WD, ed. Cleveland Clinic: Current Clinical Medicine. 2nd ed. Philadelphia, PA: Saunders Elsevier; 2009:985-994.
Crismon L, Argo TR, Buckley PF. Schizophrenia. In: DiPiro JT, Talbert RL, Yee GC, et al, eds. Pharmacotherapy: A Pathophysiologic Approach, 9th ed.New York, NY: McGraw-Hill; 2014. http://accesspharmacy.mhmedical.com/content.aspx?sectionid=45310501&bookid=689&Resultclick=2. Accessed May 3, 2016.
American Psychiatric Association. Practice guideline for the psychiatric evaluation of adults. 2nd ed, 2006. http://psychiatryonline.org/pb/assets/raw/sitewide/practice_guidelines/guidelines/psychevaladults.pdf . Accessed May 3, 2016.
American Psychiatric Association. Practice guideline for the treatment of patients with schizophrenia. 2nd ed, 2004. http://psychiatryonline.org/pb/assets/raw/sitewide/practice_guidelines/guidelines/schizophrenia.pdf. Accessed May 3, 2016.
Argo TR, Crismon ML, Miller AL, et al. Schizophrenia treatment algorithms. Texas Medication Algorithm Project Procedural Manual. 2008.
Buchanan RW, Kreyenbuhl J, Kelly Dl. The 2009 schizophrenia PORT psychopharmacological treatment recommendations and summary statements. Schizophr Bull. 2010;36(1):71-93.
Kreyenbuhl J, Buchanan RW, Dickerson FB, Dixon LB. The schizophrenia patient outcomes research team (PORT): updated treatment recommendations 2009. Schizophr Bull. 2010;36(1):94-103.
Dixon LB, Dickerson F, Bellack AS, et al. The 2009 schizophrenia PORT psychosocial treatment recommendations and summary statements. Schizophr Bull. 2010;36(1):48-70.
Seeman MV. Clinical interventions for women with schizophrenia: pregnancy. Acta Psychiatr Scand. 2013;127(1):12-22.
Substance Abuse and Mental Health Services Administration (SAMHSA). Behavioral health trends in the United States: results from the 2014 National Survey on Drug Use and Health. http://www.samhsa.gov/data/sites/default/files/NSDUH-FRR1-2014/NSDUH-FRR1-2014.pdf . Accessed May 3, 2016.
Doering PL, Li R. Substance-related disorders I: overview and depressants, stimulants, and hallucinogens. In: DiPiro JT, Talbert RL, Yee GC, et al, eds. Pharmacotherapy: A Pathophysiologic Approach. 9^th ed. New York, NY: McGraw-Hill; 2014. http://accesspharmacy.mhmedical.com/content.aspx?sectionid=45310499&bookid=689&Resultclick=2. Accessed May 3, 2016.
Nelson ME, Bryant SM, Aks SE. Emerging drugs of abuse. Emerg Med Clin N Am. 2014;32(1):1-28.
Howard MO, Bowen SE, Garland ER. et al. Inhalant use and inhalant use disorder in the United States. Addict Sci Clin Pract. 2011;6(1):18-31.
Kowalchuk A, Reed BC. Substance use disorders. In: Rakel RE, Rakel DP, eds. Textbook of Family Medicine. 9th ed. Philadelphia, PA: Saunders Elsevier; 2016:1152-1163.
Gunderson EW, Haughey HM, Ait-Daoud N, et al. "Spice" and "K2" herbal highs: a case series and systematic review of the clinical effects and biopsychosocial implications of synthetic cannabinoid use in humans. Am J Addict. 2012;21(4):320-326.

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Module 12. Psychiatric Disorders

The following common psychiatric disorders are discussed within this module:

Introduction

MAJOR DEPRESSIVE DISORDER

Overview

Treatment Recommendations

Special Populations

Monitoring Parameters

BIPOLAR DISORDER

Overview

Treatment Recommendations

Special Populations

Monitoring Parameters

ANXIETY DISORDERS

Overview

Treatment Recommendations

Monitoring Parameters

SLEEP DISORDERS

INSOMNIA AND RELATED DISORDERS

Overview

Treatment Recommendations

Monitoring Parameters

NARCOLEPSY

Overview

Monitoring Parameters

SLEEP APNEA

Overview

Treatment Recommendations

EATING DISORDERS

Overview

Treatment Recommendations

Monitoring Parameters

SCHIZOPHRENIA

Overview

Treatment Recommendations

Special Populations

Monitoring Parameters

SUBSTANCE ABUSE

Overview

Treatment Recommendations

Monitoring Parameters

Focus Points For Medication Therapy Management (MTM) in Psychiatric Disorders

References

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