Antipsychotics as antidepressants

Three second‐generation antipsychotic (SGA) agents have received FDA approval for adjunctive treatment, to antidepressant, of major depressive disorder: quetiapine, aripiprazole, and olanzapine. Additionally, quetiapine and lurasidone have been approved for the treatment of bipolar depression. There are data suggesting that quetiapine is effective for major depressive disorder as monotherapy. These agents are effective for depression only at subantipsychotic doses. Receptor profiles predict that all SGA will have anxiolytic effects as subantipsychotic doses but that all will be dysphorogenic at full antipsychotic doses (i.e., produce a depression‐like clinical picture). The antidepressant effect appears to be unique to some agents, with direct evidence of insignificant antidepressant action for ziprasidone. Three general principles can guide the use of antipsychotics as antidepressants: (i) All SGAs may have anxiolytic effects; (ii) full antipsychotic doses are dysphorogenic, and therefore, subantipsychotic doses are to be used; and (iii) SGAs do not have a general antidepressant effect, rather, this appears to be unique to quetiapine and aripiprazole, and possibly lurasidone.     

Use of antidepressants in the treatment of depression in Asia: Guidelines,clinical evidence,and experience revisited

Major depressive disorder is prevalent worldwide, and only about half of those affected will experience no further episodes or symptoms. Additionally, depressive symptoms can be challenging to identify, with many patients going undiagnosed despite a wide variety of available treatment options. Antidepressants are the cornerstone of depression treatment; however, a large number of factors must be considered in selecting the treatment best suited to the individual. To help support physicians in this process, international and national treatment guidelines have been developed. This review evaluates the current use of antidepressant treatment for major depressive disorder in six Asian countries (China, Korea, Malaysia, Philippines, Taiwan, and Thailand). No remarkable differences were noted between Asian and international treatment guidelines or among those from within Asia as these are adapted from western guidelines, although there were some local variations. Importantly, a shortage of evidence‐based information at a country level is the primary problem in developing guidelines appropriate for Asia, so most of the guidelines are consensus opinions derived from western research data utilized in western guidelines. Treatment guidelines need to evolve from being consensus based to evidence based when evidence is available, taking into consideration cost/effectiveness or cost/benefit with an evidence‐based approach that more accurately reflects clinical experience as well as the attributes of each antidepressant. In everyday practice, physicians must tailor their treatment to the patient's clinical needs while considering associated external factors; better tools are needed to help them reach the best possible prescribing decisions which are of maximum benefit to patients.     

Are antidepressants effective in the acute and long-term treatment of depression? Sic et Non

The efficacy of antidepressant treatment of major depression remains a matter of controversy. A review of acute treatment studies suggests that for relatively more severe episodes of major depression, antidepressants are superior to treatment in the "placebo group;" however, there are numerous methodological confounds in the available literature. (Some recent, preliminary evidence suggests that antidepressants may also be of benefit in some less severely depressed populations).There is moderately strong evidence that, compared with placebo, maintenance antidepressant treatment reduces six-month relapse rates in major depression; however, it is less clear that antidepressants prevent actual recurrence of depression in the longer term. There is evidence of both over-use and under-use of antidepressant treatment, and there appears to be a "mismatch" between diagnosis and optimal treatment of depression in some clinical settings. Better designed studies are needed to resolve these uncertainties and to investigate such putative conditions as "oppositional tolerance" to long-term antidepressant treatment. The author advocates a conservative approach to antidepressant treatment, as well as a substantially extended "tapering" period when antidepressants are discontinued.     

Clinical research on antipsychotics in bipolar disorder

Antipsychotics are commonly used in bipolar disorder, both for acute mania and in maintenance treatment. The authors review available clinical research concerning the use of both conventional and atypical antipsychotics in bipolar disorder and present recommendations for a number of key clinical situations based on this review. They also consider a number of important related questions, including whether there is evidence for an increased risk of tardive dyskinesia (TD) in patients with bipolar disorder, the potential role for antipsychotics in the treatment of bipolar depression, the role of antipsychotics in maintenance treatment of bipolar disorder, the potential for antipsychotics to induce depression in bipolar illness, and whether antipsychotics can be considered mood stabilizers with a place as monotherapy for bipolar mania. They conclude that standard treatment for acute mania should begin with a mood stabilizer, with benzodiazepines used as an adjunct for mild agitation or insomnia and antipsychotics used as an adjunct for highly agitated, psychotic, or severely manic patients. They also conclude that atypical antipsychotics are preferable to conventional antispychotics because of their more favorable side effect profile and reduced risk of tardive dyskinesia. They review the evidence for using atypical antipsychotics as first-line monotherapy for mania and conclude that more evidence concerning the risk of TD and their efficacy as maintenance treatment in bipolar disorder is needed before a conclusion can be made. Should the eventual risk of TD associated with atypical antipsychotics be found to be minimal and their efficacy in maintenance treatment found to be high, they could eventually be considered first line monotherapy for bipolar disorder. They conclude that treatment with an antipsychotic during bipolar depression should be limited to those patients who have psychosis and that atypical antipsychotics are preferred over conventional antipsychotics in this situation, not only because of their reduced risk of side effects but also because theoretically they may have antidepressant efficacy due to their effects on the serotonin system. The clinical research findings summarized in the article are, for the most part, supported by a recently published guideline based on a consensus of clinical experts.     

Long-term continuation antidepressant treatment: a comparison study

This retrospective study examined the clinical characteristics and the course of 26 patients with major affective disorders who repeatedly relapsed during or shortly after antidepressant tapering off at the usual 6-12-month intervals. The patients apparently required long-term antidepressant continuation therapy not preventive therapy, as they were unable to be successfully tapered off antidepressants over a mean of 36.6 months. In contrast with a group of 15 randomly selected patients with a more typical recurrent course of illness and successful tapers after 6-12 months of treatment, the long-term continuation therapy patients were younger, had a longer duration of depression before entering treatment, and were more likely to meet the DSM-III criteria for concomitant dysthymic, panic, or personality disorder or major depression with psychotic features. The findings suggest that secondary Axis I and Axis II diagnoses in antidepressant-responsive depressed patients are associated with the need for long-term continuation treatment.     

The acute treatment of anxiety and depression

Anxiety and depression are commonly occurring symptoms. Anxiety disorders and mood disorders usually share common symptoms and they frequently co-exist. There is a considerable body of research that has demonstrated that anxiety and depression can be distinguished from each other at the syndrome level. There is also evidence that such a distinction is arbitrary and not well substantiated. Clinically, the practitioner is often faced with the problem of treating a patient who presents with anxiety and depressive symptoms at the same time. It is well-established that the first line of treatment in major mood disorder is the used of tricyclic antidepressant in adequate dosage. The first line of treatment for the anxiety disorders is usually the administration of benzodiazepine anxiolytics. The anti-depressants have to be given for some months to the majority of patients whereas the anxiolytics are given for short periods. The tricyclics have a relatively slow onset of action compared to the benzodiazepines. Recent evidence is available about the effectiveness of the triazolo-benzodiazepines in panic disorder with or without secondary major mood disorder. There are also reports of the effects of the triazolo-benzodiazepines in primary mood disorder. In these mood disorders, the benzodiazepines caused rapid relief of both anxious and depressive symptomatology. The effects of the benzodiazepines occur even in the presence of melancholic depression. Where anxiety and depression coexist, the clinician may wish to consider beginning anti-depressant therapy with combined tricyclic antidepressant and benzodiazepine to produce rapid symptom relief. After four weeks the benzodiazepine should be faded out and therapy continued with the tricyclic medication alone.     

Improving adherence to antidepressants: a systematic review of interventions

BACKGROUND: Effectiveness of antidepressant medication is reduced by patients' nonadherence. Several interventions to improve adherence in patients diagnosed with unipolar depression have been tested. OBJECTIVE: To systematically review the effectiveness of interventions that aimed to improve adherence to antidepressant medication in patients with unipolar depression. METHOD: Systematic review of English-language articles of randomized controlled trials obtained by a computerized literature search of MEDLINE (1966-January 2002) using the terms patient compliance, patient dropout, treatment refusal, patient education, adherence, clinical trial, randomized controlled trial, controlled trial, depressive disorder, and depression; PSYCINFO (1984-January 2002) using the terms random, clinical, control, trial, adherence, compliance, noncompliance, dropouts, patient education, depression, major depression, affective disorders, and dysthymic disorder; EMBASE (1980-January 2002) using the terms patient compliance, patient dropouts, illness behavior, treatment refusal, patient education, clinical trial, controlled study, randomized controlled trial, and depression; and the Cochrane Controlled Trials Register (no restrictions) using the terms random*, complian*, adheren*, pharmacotherapy, regimen*, educat*, medicat*, depression, and depressive disorder. RESULTS: Educational interventions to enhance adherence failed to demonstrate a clear benefit on adherence and depression outcome. However, collaborative care interventions tested in primary care demonstrated significant improvements in adherence during the acute and continuation phase of treatment and were associated with clinical benefit, especially in patients suffering from major depression who were prescribed adequate dosages of antidepressant medication. CONCLUSION: We found evidence to support the introduction of interventions to enhance adherence with antidepressant medication in primary care, not only because of better adherence but also because of better treatment results. Because collaborative care interventions require additional resources, a better understanding of the mode of action of different programs is needed to reduce avoidable costs. The effectiveness of educational interventions needs more evidence.     

Texas Children's Medication Algorithm Project: update from Texas Consensus Conference Panel on Medication Treatment of Childhood Major Depressive Disorder

OBJECTIVE: To revise and update consensus guidelines for medication treatment algorithms for childhood major depressive disorder based on new scientific evidence and expert clinical consensus when evidence is lacking. METHOD: A consensus conference was held January 13-14, 2005, that included academic clinicians and researchers, practicing clinicians, administrators, consumers, and families. The focus was to review, update, and incorporate the most current data to inform and recommend specific pharmacological approaches and clinical guidance for treatment of major depressive disorder in children and adolescents. RESULTS: Consensually agreed on medication algorithms for major depression (with and without psychosis) and comorbid attention-deficit disorders were updated. These revised algorithms also incorporated approaches to address issues of suicidality, aggression, and irritability. Stages 1, 2, and 3 of the algorithm consist of selective serotonin reuptake inhibitor and norepinephrine serotonin reuptake inhibitor medications whose use is supported by controlled, acute clinical trials and clinical experience. Recent studies provide support that selective serotonin reuptake inhibitors in addition to fluoxetine are still encouraged as first-line interventions. The need for additional assessments, precautions, and monitoring is emphasized, as well as continuation and maintenance treatment. CONCLUSIONS: Evidence and expert clinical consensus support the use of selected antidepressants in the treatment of depression in youths. The use of the recommended antidepressant medications requires appropriate monitoring of suicidality and potential adverse effects and consideration of other evidence-based treatment alternatives such as cognitive behavioral therapies.     

Antidepressant treatment in the primary care office: outcomes for adjustment disorder versus major depression.

BACKGROUND: Antidepressants are widely used by primary care physicians. Very little comparative data exists regarding the newer antidepressants in regards to efficacy in naturalistic primary care outpatient settings where the treatment of adjustment disorder and major depressive disorder is concerned. Our objective was to determine if there is a difference in antidepressant effectiveness between disorders in the newer antidepressants (SSRIs) in a primary care setting when a formal systematic depression treatment protocol is used. METHOD: A retrospective review of 63 major depression patients and 33 adjustment disorder patients in a primary care setting was undertaken. Patients had been prescribed mostly SSRIs. DSM-IV symptoms, PHQ-9 depression rating scale scores, and functional disability reports were systematically used to evaluate partial and full remission from patients' depressive states. RESULTS: Neither depressed patients, nor adjustment disordered patients demonstrated a difference in clinical response to any particular antidepressant. The main statistical difference was in response rates, where patients diagnosed with adjustment disorder were twice as likely to respond to standard antidepressant treatment as depressed patients. This retrospective database design with moderate sample size limits the statistical power of this study. CONCLUSION: Antidepressants are very effective in treating depression in the primary care setting and may even be an effective and efficient treatment for adjustment disorder with depressed mood.     

The roles of BDNF in the pathophysiology of major depression and in antidepressant treatment

Neurotrophic factors are critical regulators of the formation and plasticity of neuronal networks. Brain-derived neurotrophic factor (BDNF) is abundant in the brain and periphery, and is found in both human serum and plasma. Animal studies have demonstrated that stress reduces BDNF expression or activity in the hippocampus and that this reduction can be prevented by treatment with antidepressant drugs. A similar change in BDNF activity occurs in the brain of patients with major depression disorder (MDD). Recently, clinical studies have indicated that serum or plasma BDNF levels are decreased in untreated MDD patients. Antidepressant treatment for at least four weeks can restore the decreased BDNF function up to the normal value. Therefore, MDD is associated with impaired neuronal plasticity. Suicidal behavior can be a consequence of severe impaired neuronal plasticity in the brain. Antidepressant treatment promotes increased BDNF activity as well as several forms of neuronal plasticity, including neurogenesis, synaptogenesis and neuronal maturation. BDNF could also play an important role in the modulation of neuronal networks. Such a neuronal plastic change can positively influence mood or recover depressed mood. These alterations of BDNF levels or neuronal plasticity in MDD patients before and after antidepressant treatment can be measured through the examination of serum or plasma BDNF concentrations. BDNF levels can therefore be useful markers for clinical response or improvement of depressive symptoms, but they are not diagnostic markers of major depression.     

Antidepressant efficacy of venlafaxine

Venlafaxine is a unique antidepressant medication with well documented efficacy and safety in the acute treatment of major depressive disorder. Reports suggest that it may also be effective in the treatment of dysthymic disorder and bipolar II depression, but the available data for these conditions are more limited compared to major depressive disorder. Several studies suggest that there may be a more rapid onset of action for venlafaxine in the treatment of major depression compared to other antidepressant pharmacotherapies, but this has not been fully established. Venlafaxine is also effective in the important long term continuation and maintenance phases of the treatment of depression.     

Evidence of early onset of antidepressant effect in randomized controlled trials

Although antidepressant medications are effective in approximately 70% of patients with major depressive disorder, they have a delayed onset of therapeutic effect. This latency is problematic in that it prolongs the impairments associated with depression, leaves patients vulnerable to an increased risk of suicide, increases the likelihood that a patient will prematurely discontinue therapy, and increases medical costs associated with severe depression. No adequately designed prospective trials have been conducted to evaluate comparative time to onset of antidepressant effect. However, evidence suggests that some antidepressant agents may begin to work faster than others. Citalopram, venlafaxine, and mirtazapine each have exhibited statistically significant differences in some measures of antidepressant action within the first 2 weeks of treatment, both in placebo-controlled trials and in head-to-head comparisons with other antidepressants. This article reviews the data that hint at these drug-specific differences in time to onset of action. Given the potential benefits of early-acting antidepressant treatments, the possibility of superior speed of onset of citalopram, venlafaxine, and mirtazapine presented here merits further study in adequately designed, prospective clinical trials.     

Efficacy of combined,sequential and crossover psychotherapy and pharmacotherapy in improving outcomes in depression

There is a growing recognition that relapse and recurrence after the successful treatment of major depression is a common and debilitating outcome that has massive social costs. Although many patients achieve a sustained recovery with maintenance pharmacotherapy, the long-term outcome for a significant proportion of patients is still poor. The purpose of this review is to evaluate the role of combined psychological and pharmacological therapies in minimizing relapse and recurrence in the treatment of depression. Three approaches have been investigated: concurrent treatment, sequential treatment and crossover treatment. Concurrent therapy is as effective as monotherapy for the treatment of mild-to-moderate depressive disorder and shows evidence of a potential treatment advantage in cases where depression is more severe. Consecutive sequencing of pharmacotherapy and psychotherapy has demonstrated some benefit for both the conversion of partial to full response and the prevention of relapse and recurrence, especially in more severely depressed patients. Crossover treatments during the maintenance phase (i.e., switching patients from one treatment to a second after an adequate response to the first) show evidence of being beneficial in preventing relapse and recurrence. Variants of cognitive therapy that have been modified to specifically address residual symptoms in patients who have recovered from depression appear to be the most effective. A review of the studies to date indicates that cognitive therapy may play a role in improving remission rates and decreasing relapse and recurrence rates. Although most studies are small, there is a consistent suggestion of superior prophylaxis for patients receiving some type of sequenced or crossover treatment in which the delivery of antidepressant medication and structured antidepressant psychotherapy is combined. These approaches warrant greater attention; they may present another route for enhancing long-term recovery from major depression.     

Poststroke depression: prevalence, diagnosis, treatment, and disease progression.

In recent years, poststroke depression has attracted worldwide interest. This review focuses on the major research themes that have emerged. Pooled data from studies conducted throughout the world have found prevalence rates for major depression of 19.3% among hospitalized patients and 23.3% among outpatient samples. The diagnosis of poststroke depression is most appropriately based on a structured mental state exam and DSM-IV criteria for depression due to stroke with major depressive-like episode or depressive features. Rarely, poststroke patients may also develop bipolar mood disorder. The treatment of poststroke depression has been examined in several placebo-controlled randomized clinical trials with both nortriptyline and citalopram showing efficacy. The progression of recovery following stroke can be altered by treating depression, which has been shown to improve recovery in activities of daily living and cognitive impairment and to decrease mortality. In addition, two studies have demonstrated that poststroke depression can be prevented using antidepressant medication, which also decreases the frequency of associated physical illness. Furthermore, two studies have shown that premorbid depression can significantly increase the risk of stroke over the subsequent 10-15 years. The mechanisms underlying the association of cerebrovascular diseases and mood disorder are important areas for future investigation.     

Antidepressants and their onset of action: a major clinical, methodological and pronostical issue

Although antidepressant medications are effective in about 50-70% of patients with major depressive disorder (MDD), they have a delayed onset of therapeutic effect. This latency is one of the current major limitations of these medications, in that it prolongs the impairments associated with depression, leaves patients vulnerable to an increased risk of suicide, increases the likelihood that a patient will prematurely discontinue therapy, and increases medical costs associated with severe depression. It is becoming increasingly clear that differences may exist between antidepressants and some evidence suggests that some antidepressant agents may begin to work faster than others. Escitalopram, duloxetine, venlafaxine, and mirtazapine have shown statistically significant differences in some measures of antidepressant action within the first two weeks of treatment, both in placebo-controlled trials and in head-to-head comparisons with other antidepressants. Results of the current review should be regarded with certain important limitations in mind. First, differences in times to onset of antidepressant response have been shown in clinical efficacy studies not specifically designed to detect differences in onset of action (post-hoc analysis). Second, results observed in 'pure' clinical trial samples should not be directly generalized to the real clinical practice since it has been proven in clinical settings that less than one in seven depressed patients would be eligible to participate in antidepressant clinical trials. For instance, depressed patients who are suicidal or who score higher than 30 on the 17-item HAM-D are excluded from antidepressant clinical trials. Third, caution is warranted when applying these findings to clinical populations with more severe depressions with respect to the fact that among clinical populations, severity of depression coincides with comorbidity, including such psychiatric disorders as anxiety disorders, personality disorders and substance abuse. In addition, the magnitudes of the size-effects of antidepressants versus placebo are clearly higher in severely depressed patients. Fourth, specific items on depression rating scales may induce greater antidepressant/placebo differences. For instance, the 17-item HAM-D contains three questions pertaining to sleep. It questions the fact that earlier onset may appear not only via a specific antidepressant effect but also via a non-specific effect on anxiety, sleep, physical pain or other accessory symptoms. Thus, current data do not clearly support claims that one drug reduces the symptoms of depression faster than another, though the existing literature suggests that escitalopram displays some superiority in terms of rapidity of action. Given the potential benefits of early-acting antidepressant treatments, the possibility of superior speed of onset of escitalopram presented here merits further study in adequately designed, prospective clinical trials. A definitive demonstration of early onset of action awaits the results of appropriately designed and powered clinical studies, which may include (1) a prospective definition of early onset of action, (2) more focused assessments of core emotional symptoms and cognitive deficits of depression by using specific and sensitive tools, (3) a data-analytic approach capable of capturing the dynamic nature of symptomatic change (for example, survival analysis), and (4) strategies to minimize biases and heterogeneity of response.     

Double-blind, placebo-controlled, fixed dose trial of minaprine in patients with major depression

Minaprine dihydrochloride is a novel psychotropic drug possessing both antidepressant and psycho-stimulant properties. Prior clinical studies have shown minaprine to be as effective as standard antidepressant agents in the treatment of endogenous depression. The present study examined the safety and efficacy of minaprine at four different doses compared to placebo in 190 outpatients with major depression. Overall, minaprine demonstrated a significant antidepressant action compared to placebo, which was most evident at the maximum dose of 400 mg daily. These data, together with a favorable side effects profile, suggest that minaprine may be an effective antidepressant agent for the treatment of major depression.     

Major depression in childhood and adolescence

Major depression in children and adolescents is diagnosed by the same criteria used in the adult disorder. There is a depth of knowledge regarding the childhood disorder in the areas of natural history, comorbidity, prognosis, epidemiology, and treatment. There are no controlled studies on the efficacy of psychotherapy for the treatment of childhood depression and only a few controlled studies on the efficacy of pharmacologic therapy. Current clinical practice combines individual psychotherapy, family intervention and education, and tricyclic antidepressant therapy in doses of 2 to 5 mg/kg to yield serum levels greater than 200 ng/ml for the treatment of major depression in children. Electrocardiograms should be performed prior to each increase in dose. Mood and cognitive functioning rapidly return to baseline levels following appropriate treatment but interpersonal difficulties tend to remain after resolution of the depression.     

The role of inflammatory mediators in the biology of major depression: central nervous system cytokines modulate the biological substrate of depressive symptoms, regulate stress-responsive systems, and contribute to neurotoxicity and neuroprotection.

Depression represents a major public health problem. It is estimated that 13-20% of the population has some depressive symptoms at any given time and about 5% of the population is assumed to suffer from major depression. Known pathological processes include ischemia, neoplasia, necrosis, apoptosis, infection, and inflammation. Of those, inflammation is the most compatible with the waxing and waning course of depression, and could explain the biology of this disorder that has a fluctuating course with severe episodes that can be followed by partial or complete remission. Over the years a body of evidence has been accumulated suggesting that major depression is associated with dysfunction of inflammatory mediators. Major depression commonly co-occurs with ischemic heart disease and decreased bone mineral density. Depressive symptoms are known to have a negative impact on cardiovascular prognosis, increasing the mortality rate of coronary artery disease. Several lines of evidence indicate that brain cytokines, principally interleukin-1beta (IL-1beta) and IL-1 receptor antagonist may have a role in the biology of major depression, and that they might additionally be involved in the pathophysiology and somatic consequences of depression as well as in the effects of antidepressant treatment. A particularly unique and novel aspect of the studies and views discussed here is their potential to lead to interventions which may reduce the morbidity and mortality risks for osteoporosis, cardiovascular disease, and behavioral symptoms in patients with major depression. We also discuss the emerging concept of peripheral and central cytokine compartments: their integration and differential regulation is a key element for the optimal functioning of the immune and nervous systems.     

The opposite effects of fluvoxamine and sertraline in the treatment of psychotic major depression: a case report

Background  

Psychotic major depression is a clinical subtype of major depressive disorder. A number of clinical studies have demonstrated the efficacy of the combination of an antidepressant (for example, a tricyclic antidepressant or selective serotonin reuptake inhibitor (SSRI)) and an atypical antipsychotic or electroconvulsive therapy (ECT) in treating psychotic major depression. In several studies, monotherapy of SSRIs such as fluvoxamine has been shown to be effective in the treatment of psychotic major depression.     

World Federation of Societies of Biological Psychiatry (WFSBP) Guidelines for Biological Treatment of Unipolar Depressive Disorders, Part 2: Maintenance treatment of major depressive disorder and treatment of chronic depressive disorders and subthreshold depressions.

These practice guidelines for the biological treatment of unipolar depressive disorders were developed by an international Task Force of the World Federation of Societies of Biological Psychiatry (WFSBP). The goal for developing these guidelines was to systematically review all available evidence pertaining to the treatment of the complete spectrum of unipolar depressive disorders, and to produce a series of practice recommendations that are clinically and scientifically meaningful based on the available evidence. These guidelines are intended for use by all physicians seeing and treating patients with these conditions. The data used for developing these guidelines have been extracted primarily from various national treatment guidelines and panels for depressive disorders, as well as from meta-analyses and reviews on the efficacy of antidepressant medications and other biological treatment interventions identified by a search of the MEDLINE database and Cochrane Library. The identified literature was evaluated with respect to the strength of evidence for its efficacy and was then categorized into four levels of evidence (A-D). The first part of these WFSBP guidelines on unipolar depressive disorders covered the acute and continuation treatment of major depressive disorder (Bauer et al 2002). This second part of the guidelines covers the management of the maintenance-phase treatment of major depressive disorder, as well as the treatment of chronic and subthreshold depressive disorders (dysthymic disorder, double depression, minor depressive disorder and recurrent brief depression). These guidelines are primarily concerned with the biological treatment (including antidepressants, lithium, other psychopharmacological and hormonal medications, and electroconvulsive therapy) of young adults and also, albeit to a lesser extent, children, adolescents and older adults.