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June 2010

Olanzapine Long-Acting Injection
Extended-release injectable olanzapine (Zyprexa Relprevv) appears to be similar in efficacy to oral olanzapine for relapse prevention in patients with schizophrenia.

Preventing Relapse in Bipolar I Disorder: Lithium, Valproate, or the Combination?
In an open-label trial, the combination of lithium and valproate (Depakote and others) was more effective at preventing breakthrough mood episodes than valproate monotherapy in patients with bipolar I disorder.

Choosing among SSRIs: How Does Fluvoxamine Rate?
Fluvoxamine (Luvox and others) is similar to other selective serotonin reuptake inhibitors (SSRIs) in efficacy and overall tolerability for the acute treatment of major depression. Specific side effects vary among antidepressants.

In Brief
"Traditional" Diet Lowers Risk of Depression and Anxiety; ECT Benefits Patients with Chronic PTSD

Green Tea and the Risk of Depression
In a cross-sectional study, increased consumption of green tea was associated with a decreased risk of depression.

Choosing among SSRIs: How Does Fluvoxamine Rate?

June 2010

Selective serotonin reuptake inhibitors (SSRIs) are generally viewed as fairly similar to one another. How then is the clinician to choose among them? In a multiple-treatments meta-analysis, Cipriani and others found sertraline (Zoloft and others) and escitalopram (Lexapro) to have the best balance between efficacy and tolerability (BTP 2009;32:25).1 When cost was figured in, sertraline was deemed the best overall choice for first-line treatment because of its availability in a generic formulation. More recently, Omori and coauthors compared the tolerability and efficacy of fluvoxamine (Luvox and others) with other SSRIs for the treatment of depression.2

Using the Cochrane collaboration database, the authors analyzed 54 randomized controlled trials, comprising more than 5000 subjects, of antidepressants for the acute treatment of major depression. They conclude that there is no strong evidence that fluvoxamine is either superior or inferior to other antidepressants in efficacy whether response or remission is the criterion. Overall tolerability also is comparable between fluvoxamine and comparison drugs. However, confirming clinical impressions, side effect profiles differ among antidepressants. Fluvoxamine tends to cause more gastrointestinal side effects than other antidepressants. For example, it causes vomiting or nausea more than twice as often as the tricyclics imipramine (Tofranil and others), clomipramine (Anafranil and others), or amitriptyline (Elavil and others).

Pharmacokinetics also differ among SSRIs. Compared with other agents in this class, fluvoxamine plasma protein binding is relatively low at 77%. It shows nonlinear steady-state pharmacokinetics, with disproportionately higher plasma concentrations at higher doses. As with other SSRIs, there is no clear relationship between patient response or adverse effects and plasma fluvoxamine concentrations. Fluvoxamine's pharmacokinetics remain unaltered by increasing age or renal impairment. Fluvoxamine is metabolized by the hepatic cytochrome P450 (CYP) enzyme system. It has prominent affinity for the CYP1A2 isoenzyme, less affinity for CYP3A4 and CYP2C, and minimal affinity for CYP2D6. It impairs the metabolic elimination of many drugs, including tertiary amine tricyclic antidepressants, alprazolam (Xanax and others), diazepam (Valium and others), theophylline (Uniphyl), propranolol (Inderal), and possibly carbamazepine (Tegretol and others). Smoking increases CYP1A2 activity, and smokers appear to have lower serum concentrations of fluvoxamine than do nonsmokers. Fluvoxamine has no active metabolites. Its mean elimination half-life is 15 hours, and it is excreted primarily in the urine, largely as inactive metabolites.

Six SSRIs are currently available in the United States. Five come in generic formulations, which tend to be much less expensive than brand-name products. Per the earlier review by Cipriani and coworkers, sertraline is a reasonable SSRI for a first choice. Many clinicians turn to a second SSRI in their algorithm if a first SSRI is ineffective or poorly tolerated. This practice is supported by the recently accepted third version of the American Psychiatric Association's treatment guideline for major depressive disorder. If a second SSRI is to be employed, the clinician should be familiar with its properties and differences from other antidepressants.

1Cipriani A, Furukawa TA, Salanti G, Geddes JR, Higgins JP, Churchill R, Watanabe N, Nakagawa A, Omori IM, McGuire H, Tansella M, Barbui C: Comparative efficacy and acceptability of 12 new-generation antidepressants: A multiple-treatments meta-analysis. Lancet 2009;373:746-758.

2Omori IM, Watanabe N, Nakagawa A, Cipriani A, Barbui C, McGuire H, Churchill R, Furukawa TA: Fluvoxamine versus other anti-depressive agents for depression (Review). Cochrane Database Syst Rev 2010;3:CD006114.