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IN THIS ISSUE:
April 2010

Depression during Pregnancy
New guidelines aid clinicians in treating pregnant women with depression.

SSRIs versus an SNRI
A new study failed to find enhanced benefit from duloxetine (Cymbalta) compared with generic selective serotonin reuptake inhibitors in patients with depression.

Zopiclone and Morning-After Impairment
In a small trial of older adults, driving ability and cognitive performance were impaired the morning after subjects took a dose of zopiclone at bedtime.

In Brief
Antipsychotic Polypharmacy Does Not Increase Mortality Risk in Schizophrenia; Tarenflurbil Fails to Slow Cognitive Decline in Alzheimer’s Disease

Second-Generation Antipsychotics Cause Weight Gain and Adverse Metabolic Effects in Young Patients
Second-generation antipsychotics can be life-saving for youth with serious psychiatric illnesses, but they carry the risk for weight gain and possible long-term cardiovascular and metabolic problems.

SSRIs versus an SNRI

April 2010

Some meta-analyses suggest that antidepressants which block the reuptake of both serotonin and norepinephrine (serotonin-norepinephrine reuptake inhibitors [SNRIs]) can usher more depressed patients into remission than selective serotonin reuptake inhibitors (SSRIs).1,2 But prospective studies have failed to demonstrate this.3-5 A new study has similarly failed to show enhanced benefit from a branded SNRI (duloxetine [Cymbalta]) versus generic SSRIs.

Martinez et al enrolled 750 patients who were suffering from severe episodes of major depressive disorder.6 The subjects, two-thirds of whom were women, were assigned randomly to take duloxetine, 30 to 60 mg/day, or one of four generic SSRIs—citalopram (Celexa and others), sertraline (Zoloft and others), fluoxetine (Prozac and others), or paroxetine (Paxil and others)—chosen by the doctor and dosed clinically for about 3 months.

Neither the percentage of patients in remission (primary outcome determined with the Quick Inventory of Depressive Symptomatology [QIDS] scale) nor completion rates at 12 weeks were statistically greater for those treated with duloxetine (36%) than for those in the generic SSRIs group (32%). The secondary outcome measure did favor duloxetine, but duloxetine-treated subjects had significantly greater pulse rates and a higher incidence of dry mouth and constipation.

There may be some depressed patients who respond better to an SNRI than to an SSRI. And given the variability of generic products (BTP 2009;32:45),7 some patients may do better on some generic agents than others, or with a more expensive branded medicine. But for starting medication treatment with most depressed patients, generic antidepressants may be the most cost-effective strategy. As the recent analysis of Cipriani et al8 suggests (BTP 2009;32:25), sertraline might be the "best buy."

1Papakostas GI, Thase ME, Fava M, Nelson JC, Shelton RC: Are antidepressant drugs that combine serotonergic and noradrenergic mechanisms of action more effective than the selective serotonin reuptake inhibitors in treating major depressive disorder? A meta-analysis of studies of newer agents. Biol Psychiatry 2007;62:1217-1227.

2Thase ME: Are SNRIs more effective than SSRIs? A review of the current state of the controversy. Psychopharmacol Bull 2008;41:58-85.

3Kocsis JH, Thase ME, Trivedi MH, Shelton RC, Kornstein SG, Nemeroff CB, Friedman ES, Gelenberg AJ, Dunner DL, Hirschfeld RM, Rothschild AJ, Ferguson JM, Schatzberg AF, Zajecka JM, Pedersen RD, Yan B, Ahmed S, Musgnung J, Ninan PT, Keller MB: Prevention of recurrent episodes of depression with venlafaxine ER in a 1-year maintenance phase from the PREVENT study. J Clin Psychiatry 2007;68:1014-1023.

4Keller MB, Trivedi MH, Thase ME, Shelton RC, Kornstein SG, Nemeroff CB, Friedman ES, Gelenberg AJ, Kocsis JH, Dunner DL, Hirschfeld RM, Rothschild AJ, Ferguson JM, Schatzberg AF, Zajecka JM, Pedersen RD, Yan B, Ahmed S, Musgnung J, Ninan PT: The Prevention of Recurrent Episodes of Depression with Venlafaxine for Two Years (PREVENT) study: Outcomes from the 2-year and combined maintenance phases. J Clin Psychiatry 2007;68:1246-1256.

5Keller MB, Trivedi MH, Thase ME, Shelton RC, Kornstein SG, Nemeroff CB, Friedman ES, Gelenberg AJ, Kocsis JH, Dunner DL, Dunlop BW, Hirschfeld RM, Rothschild AJ, Ferguson JM, Schatzberg AF, Zajecka JM, Pedersen R, Yan B, Ahmed S, Schmidt M, Ninan PT: The Prevention of Recurrent Episodes of Depression with Venlafaxine for Two Years (PREVENT) study: Outcomes from the acute and continuation phases. Biol Psychiatry 2007;62:1371-1379.

6Martinez JM, Thase ME, Greist JH, Meyers AL, Edwards, SB, Marangell LB, Shoemaker S, Iyengar S, Swindle R: Duloxetine versus generic selective serotonin reuptake inhibitors in the treatment of a severe depressive episode. Poster presented at the 48th annual meeting of the American College of Neuropharmacology, Hollywood, FL, December 6-10, 2009.

7Chenu F, Batten L, Zernig G, Ladstaetter E, Hebert C, Blier P: Two generic antidepressant medications and their bioequivalence or bio-inequivalence. Paper presented at the 49th annual meeting of the New Clinical Drug Evaluation Unit, Hollywood, FL, June 29 - July 2, 2009.

8Cipriani 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.