Since the latest update on depression in The Lancet ,112 the results of the sequenced treatment alternatives to relieve depression (STAR*D) study113—the largest depression study ever done outside the pharmaceutical industry—have been reported. This study was a practical clinical trial with broad inclusion criteria, resulting in a highly representative sample of the US population. Undertaken in both psychiatric and primary care settings, STAR*D used up to four successive treatment steps, including a switch to and augmentation with additional drug or cognitive therapy in an equipoise randomisation design. The goal was for full remission, rather than just response. Remission rates in steps one to four were disappointing at 36·8%, 30·6%, 13·7%, and 13·0%, respectively, with a cumulative remission rate of 67% after all four steps.114 These rates were low compared with efficacy trials of antidepressants, which suggests that, in actual practice, most patients need several sequential treatment steps to achieve remission. The STAR*D trial showed no clear advantage of one strategy of drug over another for patients who did not achieve remission after one or more acute treatments. Furthermore, because there was no placebo control in this hybrid (efficacy-effectiveness) trial, there is no way to know whether any of the strategies were better than maintenance of the original treatment for an additional period. Too few patients received psychotherapy, either as an augmentation or a switch strategy, to make firm conclusions about its role.115 Neither sociodemographic nor clinical (anxious, atypical, and melancholic) features moderated the effect of various switching options after the first non-successful attempt at acute treatment. No differences in outcomes were found between primary care and psychiatric settings in the first two stages of acute treatment, suggesting that primary care physicians can be reasonable providers of care for patients with less complex depression.116
Although switching of antidepressants is a common strategy for management of depression, whether effectiveness can be improved remains controversial.117 Many combination treatment trials of antidepressant drugs or antidepressant and antipsychotic combinations have been done, but caution is warranted for the recommendation of such combinations as first-step treatments.118 One review119 also emphasises the discrepancy between practice patterns and evidence for combination therapy. Lithium carbonate continues to be used as an augmentation strategy, and second-generation anti-psychotics have been intensively studied.120,121 Drugs recommended for treatment-resistant depression are aripiprazole, quetiapine fumurate, and the combination of olanzapine with fluoxetine.
The notion of sequential combinations of pharmacotherapy or psychotherapy represents a shift in the treatment of mood disorders. Such two-stage approaches are based on awareness that one treatment strategy alone is unlikely to treat the varied symptoms of depression. Because the switch to a different treatment is dependent on the patient’s response to the first treatment, reassessment of design and methodological approaches is needed.122
Treatment of psychotic depression Patients with psychotic depression (presence of delusions or hallucinations) are often difficult to treat and need several interventions. Although new pharmacological strategies are being tested, electroconvulsive therapy is important as a frequently used and effective treatment. Antipsychotics and antidepressants are being used more often to treat psychotic depression. In two studies,123,124 the combination of an antidepressant with an antipsychotic showed greater efficacy than did the antidepressant alone.
Since the latest update on depression in The Lancet ,112 the results of the sequenced treatment alternatives to relieve depression (STAR*D) study113—the largest depression study ever done outside the pharmaceutical industry—have been reported. This study was a practical clinical trial with broad inclusion criteria, resulting in a highly representative sample of the US population. Undertaken in both psychiatric and primary care settings, STAR*D used up to four successive treatment steps, including a switch to and augmentation with additional drug or cognitive therapy in an equipoise randomisation design. The goal was for full remission, rather than just response. Remission rates in steps one to four were disappointing at 36·8%, 30·6%, 13·7%, and 13·0%, respectively, with a cumulative remission rate of 67% after all four steps.114 These rates were low compared with efficacy trials of antidepressants, which suggests that, in actual practice, most patients need several sequential treatment steps to achieve remission. The STAR*D trial showed no clear advantage of one strategy of drug over another for patients who did not achieve remission after one or more acute treatments. Furthermore, because there was no placebo control in this hybrid (efficacy-effectiveness) trial, there is no way to know whether any of the strategies were better than maintenance of the original treatment for an additional period. Too few patients received psychotherapy, either as an augmentation or a switch strategy, to make firm conclusions about its role.115 Neither sociodemographic nor clinical (anxious, atypical, and melancholic) features moderated the effect of various switching options after the first non-successful attempt at acute treatment. No differences in outcomes were found between primary care and psychiatric settings in the first two stages of acute treatment, suggesting that primary care physicians can be reasonable providers of care for patients with less complex depression.116Although switching of antidepressants is a common strategy for management of depression, whether effectiveness can be improved remains controversial.117 Many combination treatment trials of antidepressant drugs or antidepressant and antipsychotic combinations have been done, but caution is warranted for the recommendation of such combinations as first-step treatments.118 One review119 also emphasises the discrepancy between practice patterns and evidence for combination therapy. Lithium carbonate continues to be used as an augmentation strategy, and second-generation anti-psychotics have been intensively studied.120,121 Drugs recommended for treatment-resistant depression are aripiprazole, quetiapine fumurate, and the combination of olanzapine with fluoxetine.The notion of sequential combinations of pharmacotherapy or psychotherapy represents a shift in the treatment of mood disorders. Such two-stage approaches are based on awareness that one treatment strategy alone is unlikely to treat the varied symptoms of depression. Because the switch to a different treatment is dependent on the patient’s response to the first treatment, reassessment of design and methodological approaches is needed.122Treatment of psychotic depression Patients with psychotic depression (presence of delusions or hallucinations) are often difficult to treat and need several interventions. Although new pharmacological strategies are being tested, electroconvulsive therapy is important as a frequently used and effective treatment. Antipsychotics and antidepressants are being used more often to treat psychotic depression. In two studies,123,124 the combination of an antidepressant with an antipsychotic showed greater efficacy than did the antidepressant alone.
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Since the latest update on depression in The Lancet ,112 the results of the sequenced treatment alternatives to relieve depression (STAR*D) study113—the largest depression study ever done outside the pharmaceutical industry—have been reported. This study was a practical clinical trial with broad inclusion criteria, resulting in a highly representative sample of the US population. Undertaken in both psychiatric and primary care settings, STAR*D used up to four successive treatment steps, including a switch to and augmentation with additional drug or cognitive therapy in an equipoise randomisation design. The goal was for full remission, rather than just response. Remission rates in steps one to four were disappointing at 36·8%, 30·6%, 13·7%, and 13·0%, respectively, with a cumulative remission rate of 67% after all four steps.114 These rates were low compared with efficacy trials of antidepressants, which suggests that, in actual practice, most patients need several sequential treatment steps to achieve remission. The STAR*D trial showed no clear advantage of one strategy of drug over another for patients who did not achieve remission after one or more acute treatments. Furthermore, because there was no placebo control in this hybrid (efficacy-effectiveness) trial, there is no way to know whether any of the strategies were better than maintenance of the original treatment for an additional period. Too few patients received psychotherapy, either as an augmentation or a switch strategy, to make firm conclusions about its role.115 Neither sociodemographic nor clinical (anxious, atypical, and melancholic) features moderated the effect of various switching options after the first non-successful attempt at acute treatment. No differences in outcomes were found between primary care and psychiatric settings in the first two stages of acute treatment, suggesting that primary care physicians can be reasonable providers of care for patients with less complex depression.116
Although switching of antidepressants is a common strategy for management of depression, whether effectiveness can be improved remains controversial.117 Many combination treatment trials of antidepressant drugs or antidepressant and antipsychotic combinations have been done, but caution is warranted for the recommendation of such combinations as first-step treatments.118 One review119 also emphasises the discrepancy between practice patterns and evidence for combination therapy. Lithium carbonate continues to be used as an augmentation strategy, and second-generation anti-psychotics have been intensively studied.120,121 Drugs recommended for treatment-resistant depression are aripiprazole, quetiapine fumurate, and the combination of olanzapine with fluoxetine.
The notion of sequential combinations of pharmacotherapy or psychotherapy represents a shift in the treatment of mood disorders. Such two-stage approaches are based on awareness that one treatment strategy alone is unlikely to treat the varied symptoms of depression. Because the switch to a different treatment is dependent on the patient’s response to the first treatment, reassessment of design and methodological approaches is needed.122
Treatment of psychotic depression Patients with psychotic depression (presence of delusions or hallucinations) are often difficult to treat and need several interventions. Although new pharmacological strategies are being tested, electroconvulsive therapy is important as a frequently used and effective treatment. Antipsychotics and antidepressants are being used more often to treat psychotic depression. In two studies,123,124 the combination of an antidepressant with an antipsychotic showed greater efficacy than did the antidepressant alone.
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