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August 2008

High-Dose Olanzapine in Treatment-Resistant Schizophrenia
For some treatment-resistant patients with schizophrenia, high-dose olanzapine might be a better option than clozapine.

Increased Stroke Risk in Schizophrenia Patients
Patients with schizophrenia appear to have an increased risk of stroke, and the risk may be higher for women than for men.

Tamoxifen for Mania?
Through inhibition of protein kinase C, tamoxifen may benefit patients with mania and merits further study.

In Brief
Genetic Variations in Patients with Schizophrenia; Zonisamide for Weight Loss in Bipolar Disorder; Music Therapy for Stroke Recovery

NMS in Children and Adolescents
The neuroleptic malignant syndrome is a risk in children and adolescents treated with second-generation antipsychotics.

Options for SSRI-Resistant Depression in Adolescents
In a study by Brent et al, depressed adolescents who did not respond sufficiently to an SSRI benefited from switching to a different antidepressant and cognitive behavioral therapy.

Options for SSRI-Resistant Depression in Adolescents

August 2008

Only a minority of depressed patients will achieve remission with a first antidepressant. This appears at least as true for adolescents as for adults. A trial sponsored by the National Institute of Mental Health addressed the question of what to do with a depressed adolescent who has not improved adequately with a selective serotonin reuptake inhibitor (SSRI).1

Brent and associates studied patients, aged 12 to 18 years, with moderately severe and chronic major depressive disorder, who had responded insufficiently to 8 weeks of SSRI treatment at therapeutic doses. In double-blind fashion, subjects were randomly assigned to one of four different approaches for 12 weeks: (1) switch to a second, different SSRI (paroxetine [Paxil and others], citalopram [Celexa and others], or fluoxetine [Prozac and others]), 20 to 40 mg/day; (2) switch to one of the above different SSRIs plus cognitive behavioral therapy (CBT); (3) switch to venlafaxine (Effexor and others), 150 to 225 mg/day; or (4) switch to venlafaxine plus CBT.

Of patients who received CBT along with a different antidepressant, 54.8% responded versus 40.5% of those who took medication alone (P = .009). There was no difference in response rate between switching to venlafaxine or to a second SSRI. With venlafaxine, there were greater increases in diastolic blood pressure and pulse and more skin problems, mostly itching and rash.

The authors' conclusions are straightforward. If an adolescent suffering from depression fails to respond to an initial SSRI, switch to a different antidepressant. Concomitant treatment with CBT offered more benefit than a second antidepressant alone.

1Brent D, Emslie G, Clarke G, Wagner KD, Asarnow JR, Keller M, Vitiello B, Ritz L, Iyengar S, Abebe K, Birmaher B, Ryan N, Kennard B, Hughes C, DeBar L, McCracken J, Strober M, Suddath R, Spirito A, Leonard H, Melhem N, Porta G, Onorato M, Zelazny J: Switching to another SSRI or to venlafaxine with or without cognitive behavioral therapy for adolescents with SSRI-resistant depression. The TORDIA randomized controlled trial. JAMA 2008;299:901-913.