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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.⁴ Other 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.

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 Depression Rating Scale (HAM-D or HDRS), the Beck Depression Inventory (BDI), the Montgomery-Asberg Depression Rating Scale (MADRS), the Zung Self-Rating Depression Scale (ZSDS), and others. These scales generally consist of clinician- or patient-rated questions or items and provide a numeric scoring of MDD severity.

MDD 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.⁹ The 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 current symptoms of depression and prevention of relapse or recurrence of symptoms.¹⁰ Treatment of MDD is generally divided into 3 phases: acute, continuation, and maintenance.^9,10 During the acute phase of treatment (6-12 wks), remission of symptoms is the goal, along with a return to normal activities. For the continuation phase (4-9 months), prevention of relapse is the goal. For the maintenance phase (12-36 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), psychotherapy, and physical activity are the 3 main nonpharmacologic therapies used in the treatment of MDD. Electroconvulsive therapy is generally reserved for patients with severe MDD not responsive to psychotherapeutic and/or pharmacologic therapies, for patients where a rapid response is needed (eg, suicidal patients), for those with psychotic symptoms in addition to MDD, and for patients with preference for this type of therapy.^9,10 Physical activity is also an appropriate addition to the treatment plan for MDD due to its role in greater remission rates.¹⁰

Psychotherapy consists of cognitive-behavioral therapy, interpersonal therapy, psychodynamic 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.^11-13 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.

Once treatment with an antidepressant has been initiated, between 4 and 8 weeks of treatment is needed to fully assess response.⁹ If 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.¹¹ Patients who do not respond after receiving 2 or more appropriate medication trials may require adjunctive therapy, for example a second-generation antipsychotic (SGA; eg, 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.^14,15 Treatment 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.

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 and circuit 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 in between.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 the 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

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.¹⁸ These 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 (eg, aripiprazole, quetiapine, risperidone, or ziprasidone) may be considered as monotherapy.^18,22,23 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 (ie, panic, generalized, and social anxiety) are among the most common psychiatric disorders in the United States.²⁴ Kessler and colleagues reported a 12-month prevalence rate for anxiety disorders of 18.1%, with a lifetime prevalence of 28.8%.^25,26 A related condition, obsessive-compulsive disorder (OCD) is less common, with 12-month and lifetime prevalence rates of 1.2% and 2.3%, respectively.²⁷ 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.²⁸

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.^29,30 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 situations involving possible scrutiny by others (social).²⁹ PTSD requires a traumatic or stressful event, which the patient essentially experiences repeatedly with associated anxiety and other severe symptoms.³⁰ OCD 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.^29,30 Several theories have been suggested to explain the pathophysiology of anxiety disorders. These include alterations in the neurotransmitters in the brain (eg, norepinephrine, γ-aminobutyric acid, dopamine, and serotonin) as well as alteration in brain function and response to stimuli.^29,30 The signs and symptoms of anxiety disorders are summarized in Table 4.

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.

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.^29,30

Nonpharmacologic therapy

Nonpharmacologic therapies are important aspects of treatment of anxiety disorders.^29,30 Generalized anxiety, panic disorder, and social anxiety can often be treated with psychoeducation, short-term counseling, psychotherapy, stress management techniques, meditation, and exercise alone. Foods or other substances (eg, stimulants, alcohol, caffeine, nicotine, and diet pills) that can provoke anxiety should be avoided. Cognitive behavioral therapy is the most helpful for generalized anxiety disorder. For panic disorders, aerobic exercise and bibliotherapy are other effective interventions. For social anxiety, additional therapy may consist of self-help groups. Cognitive-behavioral approaches such as trauma-focused behavioral therapy and eye movement desensitization and reprocessing are effective for PTSD.^30,31 Stress management and psychoeducation are also used.³⁰ Behavioral therapy—as exposure-response prevention—is the preferred nonpharmacologic therapy for OCD.

Pharmacologic therapy

SSRIs and SNRIs are the main pharmacologic treatment used for anxiety disorders, including PTSD and OCD.^30,32,33 An anxiolytic effect should be seen within 4 to 6 weeks of starting treatment. A benzodiazepine may be added on a scheduled, short-term basis (3-6 mo) 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 misuse of the agent.

The expected response rates with SSRIs or SNRIs are 30% to 50%.^32,33 Patients failing to respond to initial SSRI therapy (after 6-12 wks) can be switched to another SSRI or given an SNRI.^29,30,32 Other classes of antidepressants may also be tried if SSRIs or SNRIs are not effective.^{32, 33} Antipsychotics (ie, 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.

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).

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.³⁴ However, symptoms of insomnia are more frequent, occurring in nearly half of the adult population.^35,36 A number of chronic medical conditions, including chronic pain conditions (eg, back pain, neuropathies, or arthritis), allergies, depression, chronic obstructive pulmonary disease, and digestive disorders (eg, gastroesophageal reflux or irritable bowel syndrome), have been found to increase the risk of developing insomnia.³⁷ Additionally, 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.³⁸

Insomnia is characterized by difficulties in falling asleep, difficulties in maintaining sleep, or too early awakenings.³⁹ Causes 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, psychiatric disorders, or medications.⁴⁰ Primary insomnia may result from neurochemical or structural abnormalities that cause an increase in metabolic rate, cortisol, whole-brain glucose consumption, or adrenocorticotropic hormone during periods of sleep.^39,41 This causes a hyperarousal state resulting in insomnia or sleep disturbances.

Sleep generally cycles between nonrapid eye movement (NREM) sleep and rapid eye movement (REM) sleep.⁴¹ Nonrapid eye movement sleep accounts for about 75% to 80% of sleep, with the remaining being REM sleep.⁴² NREM 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.^41,42 The sleep-wake cycle is controlled by both a homeostatic process (sleep and wakefulness durations) and circadian factors.⁴¹ 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.⁴² Patients 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.^40,42 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 recent stressful life events and concurrent psychiatric or medical conditions.

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.³⁵ The American Academy of Sleep Medicine (AASM) has published clinical guidelines for the management of insomnia in adults.^35,36 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 cognitive behavioral therapies are the main treatment approaches for both primary and secondary insomnia.^35,36 These include sleep hygiene, relaxation, stimulus control, and sleep restriction (see Table 7).⁴³ Nonpharmacologic therapies have been shown to be successful in 25% to 50% of patients.

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, anticonvulsants, orexin receptor agonists, heterocyclics, and over-the-counter products.^35,36

The AASM clinical guideline recommends a short- or intermediate-acting BzRA (eg, zaleplon, zolpidem, eszopiclone, triazolam, or temazepam) or ramelteon (a melatonin receptor agonist) as the initial pharmacologic treatment for insomnia (Table 8).^35,36 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 vs difficulty maintaining sleep. Patients not responding to initial therapy may be given an alternative agent from this group. Other medications, such as anticonvulsants or over-the-counter products, are generally not recommended because of the risk of side effects and limited efficacy data.

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.³⁵ 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.⁴⁵ Over half of the patients with narcolepsy also experience a sudden and short-lived loss of muscle tone, referred to as narcolepsy with cataplexy.⁴¹ 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.⁴³ The pathophysiology of narcolepsy is not fully known but may be related to a reduction in orexin (hypocretin), a neuropeptide secreted during waking hours.^41,43 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, disturbed sleep during the nights, and impairment in REM and NREM sleep.⁴⁰ 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 5 to 15 years old.⁴⁵ Overnight polysomnography and multiple sleep latency tests are often used to confirm the diagnosis.

Treatment Recommendations

The goal of therapy is alleviation of symptoms and return of normal daily functioning for the individual with narcolepsy.⁴⁰

Nonpharmacologic therapy

Nonpharmacologic therapy for narcolepsy consists of short daytime naps to alleviate sleepiness, regular bedtimes, keeping meals small, and avoiding alcohol.⁴¹ However, these interventions have limited effectiveness for most individuals.

Pharmacologic therapy

Several agents are available for treatment of narcolepsy.⁴⁶ Stimulants are the most frequently used pharmacotherapy, including modafinil, amphetamines, and methylphenidate. For modafinil, doses of 200 mg 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 approved for use in the treatment of narcolepsy and related disorders.⁴⁵ It 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 part of the Risk Evaluation and Mitigation Strategies (REMS) program.¹²

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 20 to 25 millions of individuals in the United States.⁴⁰ Sleep apneas can be classified as obstructive, central, or mixed. Obstructive sleep apnea (OSA), the more common of the 2 disorders, results from a collapse and obstruction of the upper airway but with a normal respiratory drive. In contrast, central sleep apnea (CSA) is associated with a reduced respiratory drive. Mixed sleep apnea presents with signs and symptoms of both central and obstructive sleep apneas. The conditions cause apnea, a cessation of breathing during sleep, which causes blood oxygen desaturation, along with daytime sleepiness and nighttime awakenings.

OSA results from both anatomical and neurological factors.^43,47 During 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.⁴⁸ Both OSAs and CSAs 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%-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.⁴³

Treatment Recommendations

Untreated, sleep apneas can result in significant morbidity and increased mortality, as well as reduced quality of life, making appropriate treatment essential.⁴⁰ 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.⁴⁰ For OSA, treatment strategies include positive airway pressure devices (continuous, bilevel, or autotitrating devices), oral appliances (eg, for mandibular repositioning), and surgery.^40,49,50 For most patients with CSA, continuous positive airway pressure is the preferred treatment of choice.⁴⁸ Supplemental oxygen may also benefit some patients. Pharmacologic therapy (eg, 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%.⁵¹ 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.⁵² Eating disorders have been broadly classified as anorexia nervosa, bulimia nervosa, and eating disorders–not otherwise specified.^51,53 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.^51,54

The pathophysiology of eating disorders has not been fully explained. However, imaging studies have revealed changes in brain mass in patients with eating disorders.⁵⁴ Dysfunction 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.⁵⁵ 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

Treatment Recommendations

Once diagnosed, part of the therapeutic goal for eating disorders is patient acceptance that an eating disorder is present.⁵⁵ 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.^51,53 Since eating disorders are more common among adolescents (although the disorder may continue into adulthood), the AAP has outlined treatment recommendations for eating disorders.⁵⁶

Nonpharmacologic therapy

Most treatment approaches for eating disorders are nonpharmacologic, using a multidisciplinary approach consisting of medical, nutritional, social, and psychological support.⁵¹ 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.⁵⁶

Pharmacologic therapy

Pharmacologic therapy has also been used for eating disorders, with stronger evidence available for bulimia nervosa than for anorexia nervosa.^51,56 Various agents have been used, including antidepressants, antipsychotics, and anticonvulsants for both anorexia nervosa and bulimia nervosa.⁵¹ 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.⁵⁶ SSRI 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 2015.⁵⁷ 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.⁵⁸ Men are affected more often than women (with about a 30%-40% higher lifetime risk) and usually exhibit symptoms about 3 to 4 years earlier than women.⁵⁹ The peak onset of schizophrenia is late adolescence or early adulthood (usually 15-24 years of age).⁵⁸ Both genetic and environmental factors have been implicated in the development of schizophrenia, with a possible greater contribution by environmental factors (eg, head injury, substance abuse, place and season of birth, and prenatal infections or obstetric complications).⁵⁹

Abnormalities in both brain structure and function have been suggested as possible causes for schizophrenia.⁵⁹ 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.⁶⁰ 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.^59,61 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, conceptual disorganization), negative (loss of interest or drive, ambivalence, alogia), and cognitive (poor attention, impaired memory, impaired executive function).⁶¹

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.⁶²

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.⁵⁹ 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).^63-66

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.⁶⁷ 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).^64,65,68 For a first-episode of schizophrenia, the TMAP recommends an SGA (eg, aripiprazole, olanzapine, quetiapine, risperidone, or ziprasidone).⁶⁴ Clozapine and first-generation antipsychotics (FGAs; eg, 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.⁶⁴ 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 regarding 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.⁶⁶ Once acute symptoms have resolved, antipsychotics should be continued as maintenance therapy to prevent relapse of acute symptoms.⁶⁵ 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.⁶⁹ 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 regarding 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).⁷⁰ For the year 2017, it was reported that 30.5 million people over the age of 12 years in the United States had used some type of illicit drug during the time surveyed. These illicit drugs included marijuana, cocaine, heroin, hallucinogens, inhalants, methamphetamine, or prescription drugs (eg, pain reliever, stimulants, tranquilizers, or sedatives). 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.

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.⁷⁴ However, 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.^71,74 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.⁷⁴ 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.⁷¹ 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.⁷⁴

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.^73,74 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.⁷¹ 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

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