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March 2008

Topiramate for Alcohol Dependence
Topiramate (Topamax) has been found to be beneficial in treating alcohol dependence.

Early Intervention for Schizophrenia: A Role for Antidepressants?
Antidepressants may reduce the transition from a prodrome of pre-psychosis to schizophrenia in vulnerable individuals.

In Brief
Duloxetine Approved for GAD; Depression in Parkinson’s Disease; Asthma Linked to Psychiatric Disorder

Adjunctive Antipsychotics for MDD
Patients with treatment-resistant major depressive disorder may benefit from the addition of second-generation antipsychotics to an antidepressant medication regimen.

Antipsychotics in Youth with Schizophrenia
Early-onset schizophrenia-spectrum disorder requires long-term antipsychotic treatment, but children and adolescents are sensitive to antipsychotic side effects and should be monitored carefully.

Early Intervention for Schizophrenia: A Role for Antidepressants?

March 2008

Over the past decade, several studies have focused on patients who have prodromal symptoms suggesting schizophrenia but not fully developed psychosis. One study combined low doses of risperidone (Risperdal) with cognitive behavioral therapy.1 A second used olanzapine (Zyprexa) alone.2 Both found that second-generation antipsychotics reduced the risk of transition to schizophrenia.

Another aspect of the prodrome that may lead to schizophrenia involves depressive symptoms. Last year, Cornblatt and others described a prospective study of adolescents considered to be in the pre-psychotic phase of schizophrenia.3 Forty-eight patients displaying attenuated positive symptoms of schizophrenia had been naturalistically treated with medication for at least 8 weeks and followed for at least 6 months. Twenty of the subjects were receiving antidepressants, and 28 were taking second-generation antipsychotics. Polypharmacy was common.

During the time they were observed, 12 adolescents (25%) developed a psychotic disorder. All 12 had been prescribed an antipsychotic. In contrast, no antidepressant-treated adolescent converted to the full schizophrenia syndrome.

In a comment in the Lancet, Fusar-Poli and coauthors call the data from Cornblatt et al "striking."4 They audited their own clinical experience and found similar results. Only 1 (8%) of 13 patients prescribed an antidepressant developed psychosis in the following 2 years. In contrast, 10 (29%) of 35 patients treated with antipsychotics subsequently became psychotic.

Both groups point out obvious caveats from these naturalistic observations. Antidepressant-treated adolescents could be a subgroup with a good prognosis. Beyond that, patients prescribed antipsychotic medications did not adhere to treatment as well as those prescribed antidepressants.

This interesting lead merits pursuit. As Dr Fusar-Poli's group observes, antidepressants are less stigmatizing than antipsychotics and generally better tolerated. If these tantalizing findings are confirmed by more rigorous research, another step will have been taken toward combating the scourge of schizophrenia.

1McGorry PD, Yung AR, Phillips LJ, Yuen HP, Francey S, Cosgrave EM, Germano D, Bravin J, McDonald T, Blair A, Adlard S, Jackson H: Randomized controlled trial of interventions designed to reduce the risk of progression to first-episode psychosis in a clinical sample with subthreshold symptoms. Arch Gen Psychiatry 2002;59:921–928.

2McGlashan TH, Zipursky RB, Perkins D, Addington J, Miller T, Woods SW, Hawkins KA, Hoffman RE, Preda A, Epstein I, Addington D, Lindborg S, Trzaskoma Q, Tohen M, Breier A: Randomized, double-blind trial of olanzapine versus placebo in patients prodromally symptomatic for psychosis. Am J Psychiatry 2006;163:790–799.

3Cornblatt BA, Lencz T, Smith CW, Olsen R, Auther AM, Nakayama E, Lesser ML, Tai JY, Shah MR, Foley CA, Kane JM, Correll CU: Can antidepressants be used to treat the schizophrenia prodrome? Results of a prospective, naturalistic treatment study of adolescents. J Clin Psychiatry 2007;68:546–557.

4Fusar-Poli P, Valmaggia L, McGuire P: Can antidepressants prevent psychosis? Lancet 2007;370:1746–1748.