Efficacy of antimanic treatments in mixed states.

OBJECTIVE: To review the efficacy of pharmacological agents in bipolar mixed states. METHODS: We conducted a PubMed search of all English-language articles involving Food and Drug Administration (FDA)-approved agents for manic/mixed states in adults with bipolar I disorder. We also included names of agents established as efficacious in acute mania/mixed states that have not received FDA approval for bipolar disorder. Bibliographies from relevant articles were also searched. The efficacy of each agent in the mixed state subpopulation was reviewed, as evidenced by change from baseline on total scores of mania [e.g., Young Mania Rating Scale (YMRS)] and depression [e.g., Montgomery-Åsberg Depression Rating Scale (MADRS)] measures. RESULTS: No available study is dedicated exclusively to the evaluation of mixed state populations. Although key inclusion and exclusion criteria are similar across treatment studies, mixed states have been variably defined and measured. The use of conventional manic and depressive metrics in bipolar mixed states perpetuates the unproven notion that mixed states are the consequence of coexisting depression and mania. Notwithstanding the methodological limitations, there are numerically more studies that exist for atypical antipsychotic agents than for any other class. On the basis of symptomatic improvement, recommendations for and/or strong admonishments against any established antimanic agents (e.g., lithium) cannot be made. An emergent signal supports combination treatment strategies (e.g., atypical antipsychotic plus divalproex) over mood stabilizer monotherapy (e.g., divalproex). Available evidence does not empirically support the hypothesis that conventional antipsychotics engender and/or amplify depressive symptoms in bipolar mixed states. CONCLUSIONS: All proven antimanic agents (including lithium), can be recommended in the treatment of mixed/dysphoric states. The totality of evidence with attention paid to the therapeutic index of each agent would suggest that atypical antipsychotics and divalproex be considered as first-line treatment, with lithium and carbamazepine as second-line. Most individuals will require combination therapy for the treatment of mixed states; variable combinations of atypical antipsychotics and conventional mood stabilizers have the most replicated evidence.

Aripiprazole for the maintenance treatment of bipolar disorder: a review of available evidence.

We aimed to review and synthesize results reporting on the maintenance efficacy of Aripiprazole in adults with bipolar I disorder. Aripiprazole is FDA approved for the acute and maintenance treatment of bipolar I disorder. Aripiprazole's efficacy during the long-term treatment of bipolar disorder is supported by extension of acute phase studies and long-term (ie, 100-week) double-blind placebo controlled recurrence prevention registration trials. Aripiprazole is not established as efficacious in the acute or maintenance treatment of bipolar depression. Moreover, aripiprazole's efficacy during the acute or maintenance phase of bipolar II disorder has not been sufficiently studied. Aripiprazole has a relatively lower hazard for metabolic disruption and change in body composition when compared to other atypical agents (eg, olanzapine, quetiapine). Moreover, aripiprazole has minimal propensity for sedation, somnolence and prolactin elevation. Aripiprazole is associated with extrapyramidal side effects, notably akathisia, which in most cases is not severe or treatment limiting. Future research vistas are to explore aripiprazole's efficacy in bipolar subgroups; recurrence prevention of bipolar depression; and in combination with other mood stabilizing agents.

The association between conventional antidepressants and the metabolic syndrome: a review of the evidence and clinical implications.

Major depressive disorder is a prevalent recurrent medical syndrome associated with inter-episodic dysfunction. The metabolic syndrome is comprised of several established risk factors for cardiovascular disease (i.e. abdominal obesity, dyslipidaemia, dysglycaemia and hypertension). The criterion items of the metabolic syndrome collectively represent a multi-dimensional risk factor for cardiovascular disease and type 2 diabetes mellitus. Extant evidence indicates that both major depressive disorder and the metabolic syndrome, albeit distinct, often co-occur and are possibly subserved by overlapping pathophysiology and causative mechanisms. Conventional antidepressants exert variable effects on constituent elements of the metabolic syndrome, inviting the need for careful consideration prior to treatment selection and sequencing. Initiating and maintaining antidepressant therapy should include routine surveillance for clinical and/or biochemical evidence suggestive of the metabolic syndrome.