Relapse prevention with antidepressant drug treatment in depressive disorders: a systematic review

Objective The longitudinal course of 51 patients with treatment-refractory bipolar disorder was examined to assess possible effects of heterocyclic antidepressants on occurrence of manic episodes and cycle acceleration
 Method
 Using criteria established from life charts, investigators rated the patients’ episodes of mania or cycle acceleration as likely or unlikely to have been induced by antidepressant therapy Discriminant function analyses were performed to assess predictors of vulnerability to antidepressant-induced mania or cycle acceleration Further, the likelihood of future antidepressant-induced episodes in persons who had had one such episode was assessed
 Results
 Thirty-five percent of the patients had a manic episode rated as likely to have been antidepressant-induced No variable was a predictor of vulnerability to antidepressant-induced mania Cycle acceleration was likely to be associated with antidepressant treatment in 26% of the patients assessed Younger age at first treatment was a predictor of vulnerability to antidepressant-induced cycle acceleration Forty-six percent of patients with antidepressant-induced mania, but only 14% of those without, also showed antidepressant-induced cycle acceleration at some point in their illness
 Conclusions
 Mania is likely to be antidepressant-induced and not attributable to the expected course of illness in one-third of treatment-refractory bipolar patients, and rapid cycling is induced in one-fourth Antidepressant-induced mania may be a marker for increased vulnerability to antidepressant- induced cycle acceleration Antidepressant-induced cycle acceleration (but not antidepressant- induced mania) is associated with younger age at first treatment and may be more likely to occur in women and in bipolar II patients
 (Am J Psychiatry 1995; 152:1130-1138)

Antidepressant-induced mania and cycle acceleration: a controversy revisited.

Objective: Psychotropic drugs often induce weight gain, leading to discomfort and discontinuation of treatment and, more importantly, increasing the risk of obesity-related illnesses such as diabetes mellitus, hypertension, and coronary heart disease. There is evidence that antidepressant drugs may induce a variable amount of weight gain, but results are sparse and often contradictory. Data Sources: We performed a literature search using the MEDLINE, ISI Web of Knowledge, and Cochrane research databases for all publications available to January 2009. We used the following keywords: antidepressant, psychotropic drugs, body weight, weight gain, obesity, overweight, adverse event, side effects, SSRIs, tricyclic antidepressants, and the name of each antidepressant active compound together with body weight or other keywords. Studies reporting body weight changes during treatment with different antidepressants were selected for eligibility. Finally, 116 studies were included in the analysis. Data Extraction: Weight change mean and standard deviation and size of each group were recorded. Missing means and standard deviations were directly calculated by using information available in the article when possible. Non-placebo-controlled studies were compared to a virtual placebo sample, whose mean and standard deviation were derived by the weighted mean of means and standard deviations of all placebo samples. Methodological quality of studies, heterogeneity, publication bias, and effect of treatment duration were systematically controlled. Data Synthesis: Quantitative results evidenced that amitriptyline, mirtazapine, and paroxetine were associated with a greater risk of weight gain. In contrast, some weight loss occurs with fluoxetine and bupropion, although the effect of fluoxetine appears to be limited to the acute phase of treatment. Other compounds have no transient or negligible effect on body weight in the short term. However, the effect of each antidepressant may vary greatly depending on an individual's characteristics and generally became more evident in the long term to a variable degree across compounds. Conclusions: Despite the fact that some analyses were done on only a few studies due to the difficulty of finding reliable information in literature, to our knowledge, this is the first comprehensive meta-analysis to allow comparison of different antidepressants as regards their impact on body weight. Data presented may be helpful for a more accurate treatment selection in patients at risk of obesity or related medical illness.

Antidepressants and Body Weight: A Comprehensive Review and Meta-Analysis

Vagus nerve stimulation (VNS) for major depressive episodes: One year outcomes

A major problem for the practitioner is the lack of satisfactory guidelines as to how long continuation drug treatment of depressive episodes must be maintained to ensure that the episode is over. This often leads to either premature withdrawal of the drug and subsequent relapse or unnecessarily prolonged treatment. Results from a collaborative project of the National Institute of Mental Health provide the first study-derived guidelines on the length of continuation therapy. Findings indicate that withdrawal of such therapy is safe only after the patient has been free of significant symptoms for 16 to 20 weeks and that focusing on mild as well as severe symptoms is critical in this decision.

Continuation drug therapy for major depressive episodes: how long should it be maintained?

Thirty-two patients who had responded to amitriptyline (150 mg daily) when suffering from a depressive illness were allocated either to receive placebo or to remain on the same medication for one year. Plasma concentrations of the drug were regularly estimated. There was no correlation between plasma concentration and subsequent residual affective morbidity. In spite of considerable encouragement, three of the patients did not take the prescribed amitriptyline and they all relapsed. Five out of sixteen patients who received placebo relapsed. None of the patients who continued to take amitriptyline relapsed. It is emphasized that the patients studied were selected, inasmuch as they were apparent responders to amitriptyline. It is concluded that this group of patients should continue to be treated with antidepressant medication for eight months after apparent recovery, and care should be taken to ensure the patients' compliance.

Continuation therapy with amitriptyline in depression.

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Continuation therapy with amitriptyline in depression.