Treatments for Eating Disorders

A very substantial number of well-designed studies (Type 1 and Type 2) have shown that manual-based cognitive-behavioral therapy (CBT) is currently the treatment of choice for bulimia nervosa (BN); roughly half of patients receiving CBT cease binge eating and purging. Well accepted by patients, CBT is the most effective means of eliminating the core features of the eating disorder and is often accompanied by improvement in psychological problems such as low self-esteem and depression; long-term maintenance of improvement is reasonably good. A large number of good to excellent outcome studies (Type 1 and Type 2) suggest that different classes of antidepressant drugs produce significantly greater reductions in the short term for binge eating and purging in BN patients than a placebo treatment; the long-term effects of antidepressant medication on BN remain untested. There is little evidence that combining CBT with antidepressant medication significantly enhances improvement in the core features of BN, although it may aid in treating comorbid anxiety and depression. The continuing paucity of controlled research on outcomes of treatment for anorexia nervosa (AN) contrasts sharply with the quantity and quality of research on outcomes of treatment for BN and binge-eating disorder (BED). Nevertheless, a specific form of family therapy, referred to as the Maudsley Model, has shown promising effects on AN in adolescent patients, although this remains to be shown to be a specific effect. Several different psychological treatments appear equally effective in reducing the frequency of binge eating in the short term in BED; these treatments include CBT, interpersonal therapy (IPT), behavioral weight loss programs, and guided self-help based on cognitive-behavioral principles. To date, only CBT and IPT have been shown to have significant longer term effects in eliminating binge eating. Evidence on the specific effects of antidepressant medication on BED is mixed. As yet, there has been no research on the treatment of the most common eating disorder diagnosis, “eating disorder not otherwise specified.”

Treatments for Pathological Gambling and Other Impulse Control Disorders

Several controlled outcome studies (Type 1 and Type 2) suggest that specific behavioral (e.g., cognitive-behavioral therapy [CBT]) and pharmacological (e.g., naltrexone, nalmefene, lithium) treatments significantly reduce the symptoms of pathological gambling in the short term compared with wait-list or placebo. Although long-term effects of manual-based CBT have been observed in several small studies, the long-term benefits of pharmacological treatment have not been adequately tested. No studies combining behavioral and pharmacological therapies have been published to date. Thus, the potential benefit of combining behavioral and drug treatments for pathological gambling remains to be investigated systematically. Although several studies (Type 1 and Type 2) suggest that CBT is effective for trichotillomania, pharmacological treatment studies for this disorder have shown mixed results. Similarly, controlled pharmacological studies (Type 1 and Type 2) of compulsive buying have demonstrated mixed results. Limited treatment studies exist for other impulse control disorders (kleptomania, intermittent explosive disorder), although various pharmacological and psychological treatments have shown promise in uncontrolled studies.

Psychosocial Treatments for Bipolar Disorder

Whereas pharmacological interventions remain the primary treatment for bipolar disorder, adjunctive psychosocial interventions have the potential to increase adherence to medication regimens, decrease hospitalizations and relapses, improve quality of life, and enhance mechanisms for coping with stress. Controlled studies have established that individual, family, and group psychoeducation, designed to provide information to bipolar patients and their families about the disorder, its pharmacological treatment, and the treatments’ side effects, leads to lower rates of recurrence and greater adherence to pharmacological treatment among bipolar patients. Type 1 and 2 studies have evaluated cognitive behavioral therapy (CBT) as an ancillary treatment. These studies indicate that CBT is associated with better medication adherence and significantly fewer recurrences and/or rehospitalizations. One Type 1 study has evaluated the effectiveness of IPSRT (interpersonal and social rhythm therapy) for bipolar disorder. IPSRT demonstrated its greatest symptomatic effects during a maintenance treatment period, especially if bipolar patients had been successful in stabilizing their daily and nightly routines during an acute treatment period. Finally, four Type 1 studies in adult and pediatric patients have shown that marital/ family therapy may be effectively combined with pharmacotherapy to reduce recurrences and improve medication adherence and family functioning.

Psychosocial Treatments for Schizophrenia

Data from hundreds of intervention research studies validate a biopsychosocial view of treatment for schizophrenia that combines pharmacotherapy with psychosocial treatments and social support. Based on the stress-vulnerability-protective factors model, these treatments work by strengthening biological, personal, and environmental factors that protect against relapse while mitigating the stressors that adversely affect the course of schizophrenia. Psychiatric treatment and rehabilitation must be integrated in a seamless approach aimed at restoring persons with schizophrenia to their best possible level of functioning and quality of life.

Pharmacological Treatment of Schizophrenia

Schizophrenia is a chronic mental disorder with a lifetime prevalence rate of approximately 1%. The first antipsychotic drug, chlorpromazine, was introduced in 1954, followed by several similar drugs. With the later introduction of clozapine, risperidone, olanzapine, quetiapine, ziprasidone, and aripiprazole, antipsychotic drugs have come to be classified as conventional (chlorpromazine-like) or atypical (clozapine-like). Both of these broad classes of medications have been demonstrated to safely improve psychotic symptoms in the acute phase of the illness and reduce risk of relapse in the maintenance phase of treatment. The atypical antipsychotics offer hope for enhanced efficacy in the treatment of schizophrenic psychopathology with a reduced burden of extrapyramidal motor dysfunction. Because of the limited efficacy of antipsychotic medication in resolving the full range of schizophrenic psychopathology, adjunctive treatments are often used to reduce morbidity. Concomitant medications such as benzodiazepines, lithium, carbamazepine, valproic acid, antidepressants, glutamate agonists, and dopamine agonists have been used alone and in combination with antipsychotic drugs in order to improve treatment response. In this chapter, we review controlled trials of the pharmacological agents used to treat schizophrenia.

Treatments for Insomnia and Restless Legs Syndrome

Treating a chief complaint of inability to sleep is a core problem in psychiatric practice, together with treating other comorbid physical or mental disorders. The treatments for insomnia and restless legs syndrome (RLS) are well within the scope of psychiatric practice. Treatments for insomnia have been controversial over the past several decades, with practice patterns being driven partly by nonmedical influences operating in the setting of limited data. In recent years, the need to consider both cognitive-behavioral and pharmacological approaches together has become more apparent, with less insistence on strict either-or approaches. Clinical trial data clearly point to the efficacy of cognitive-behavioral approaches such as stimulus control, bed restriction, and related approaches. The literature on the short-term efficacy of benzodiazepine receptor agonists (BZRAs) as hypnotics has strengthened. There is a great amount of use of non-BZRAs as hypnotics, even though there are limited studies supporting their use. For RLS, the use of low-dose dopamine agonists has been substantially supported in Type 1 clinical trials. For iron-deficiency-induced RLS, iron replacement is strongly encouraged. Approaches such as using benzodiazepines are second-line treatments. Limited support for the use of gabapentin and carbamazepine is available, but the centuries-old approach of using opiates for the treatment of RLS remains a third-line approach.

Pharmacological Treatments for Unipolar Depression

The treatment of unipolar major depression with antidepressant medication is well established on the basis of scores of randomized placebo-controlled trials involving thousands of patients. Tricyclic antidepressants (TCAs) were the first to be studied extensively; meta-analyses of placebo-controlled trials show them to be consistently and significantly more efficacious than a placebo. Because of a narrow safety margin and significant drug-induced adverse side effect problems, TCAs have now largely been replaced as the first-line treatment of depression by selective serotonin reuptake inhibitors (SSRIs)—fluoxetine, sertraline, paroxetine, citalopram, and escitalopram; serotonin norepinephrine reuptake inhibitors (SNRIs)—venlafaxine and duloxetine; as well as other compounds, including, for example, bupropion and mirtazapine. Each of these agents has been shown to be superior to a placebo and as effective as comparator TCAs or SSRIs in controlled trials. Clinical trials consistently show them to be better tolerated than TCAs, and they clearly have a wider margin of safety. However, there is a controversy concerning whether TCAs are more effective than SSRIs for the treatment of the most severely ill depressed patients. Monoamine oxidase inhibitors (MAOIs), while also more effective than placebo, have generally been reserved for treatment-refractory patients; however, a recently released transdermally delivered selegiline may be used in less refractory patients. It is now generally recognized that patients with recurrent major depression benefit from continued antidepressant treatment, and there is evidence that TCAs, SSRIs, SNRIs, and so forth are all effective for the long-term management of recurrent major depression. An important issue in evaluating the antidepressant literature is to distinguish between response rated as a reduction in the level of symptoms on a rating scale and response rated as true remission from illness.

Psychosocial Treatments for Substance Use Disorders

Our review of the literature indicates that among the most effective treatments for alcohol and illicit drug use disorders are cognitive-behavioral treatments, community reinforcement and contingency management approaches, 12-step facilitation and 12-step treatment, behavioral couples and family treatment, and motivational enhancement interventions. Most of these treatment modalities address not only drinking and/or drug use behavior but also patients’ life contexts, sense of self-efficacy, and coping skills; motivational interventions focus primarily on attempts to enhance individuals’ commitment to behavior change. Consistent with motivational interviewing principles, therapists who are interpersonally skilled, empathic, and less confrontational produce better patient outcomes, probably because they establish better therapeutic alliances with their patients. An effective strategy for many patients may be to provide lower intensity treatment for a longer duration—that is, treatment sessions spread at a lower rate over a longer period to match better the chronic, relapsing nature of many individuals’ substance use disorders. At this point, it seems wise to restrict brief interventions as a stand-alone treatment to patients with mild to moderate disorders. Longer term interventions and treatment in inpatient or residential settings should be reserved for patients with more severe, treatment-resistant substance use disorders, fewer social resources, more concomitant medical/psychiatric disorders, and a desire for longer term and/or residential treatment.

Psychopharmacological Treatments for Substance Use Disorders

The treatment of substance abuse with pharmacological agents is well established, although most experts agree that, to be successful, medication interventions must be combined with psychosocial therapies. A large number of Type 1 and Type 2 controlled trials have shown that the use of nicotine replacement therapy to induce and maintain smoking cessations significantly increases the abstinence rate. Bupropion, which is also an antidepressant, has been found in controlled trials to significantly increase the smoking abstinence rate measured at intervals up to 12 months after beginning of treatment. Trials with novel agents such as the cannabinoid receptor antagonist rimonabant and varenicline, a nicotine receptor partial agonist, have been reported at meetings but have not yet appeared in print. The treatment of alcoholism can now be enhanced by three totally different types of medications: disulfiram, which works when compliance is assured; naltrexone, which reduces alcohol reward via the endogenous opioid system and results in decreased alcohol craving and reduced drinking in most randomized clinical trials; and acamprosate, which reduces post-alcohol excitability and has been effective in European trials but less so in U.S. trials. A depot version of the opiate antagonist naltrexone was approved by the FDA in 2006. It gives therapeutic blood levels for at least 30 days and should greatly improve compliance, thus making naltrexone more useful for the treatment of both opiate addiction and alcoholism. Methadone maintenance treatment for heroin dependence has consistently shown efficacy, and the treatment options have been increased by the availability of the partial opiate agonist buprenorphine. Buprenorphine is unique in that it can be used for the treatment of opiate addiction by qualified physicians in their offices rather than requiring enrollment in a highly regulated methadone treatment program. There are as yet no FDA-approved medications for the treatment of stimulant addiction, which includes cocaine and methamphetamine. There are recent double-blind, placebo-controlled clinical trials of several medications that have been found effective against cocaine addiction and are currently in multisite trials to confirm efficacy.

Childhood Attention-Deficit/Hyperactivity Disorder: Nonpharmacological Treatments and Their Combination With Medication

Attention-deficit/hyperactivity disorder (ADHD) is a persistent disorder of childhood and adolescence that mandates early and effective intervention. Among psychosocial interventions, direct contingency management applies systematic manipulation of rewards and punishments in specialized settings. It typically yields large effects on behavior and academic performance, but (a) outcomes are often appraised through single-case experimental designs, outside the typology of clinical trials used in this volume, and (b) their effects tend not to generalize or maintain beyond the settings in which they are applied. Clinical behavior therapy involves consultation with parents and teachers regarding optimal home and school management practices. A number of Type 2 trials demonstrate the clinical value of such procedures for the behavior problems of children with ADHD as rated by parents and teachers but typically not by independent observations. Several Type 1 investigations of systematic combinations of direct contingency management plus clinical behavior therapy have yielded findings indicating significant improvements, but effects on symptoms are smaller than those found with medication. Multimodal treatment—combining intensive behavioral intervention with well-delivered pharmacological agents—does not always reveal significantly superior outcomes to medication alone, but it more consistently yields normalization of behavior patterns among children with ADHD. Further work on tailoring psychosocial interventions to ADHD-related deficits and impairments and on promoting generalized change beyond specifically targeted behaviors is urgently needed.