December 2007

High Doses of Venlafaxine
Higher doses of venlafaxine (Effexor and others) likely increase the chance of antidepressant response, but also increase the risk of side effects.

SSRIs and Bleeding Risk in Patients with Hepatitis C
The risk of selective serotonin reuptake inhibitors causing bleeding in patients with hepatitis C is modest.

Bupropion versus SSRIs for Anxiety in MDD
According to Papakostas and colleagues, bupropion (Wellbutrin and others) appears to work as well as selective serotonin reuptake inhibitors to treat anxiety in patients with major depressive disorder.

Torsades de Pointes with Haloperidol
Intravenous administration of haloperidol (Haldol and others), especially at high doses, can cause QT prolongation and torsades de pointes.

In Brief
Ziprasidone for borderline personality disorder: A negative trial; Adjunctive medications for weight loss in patients with schizophrenia or bipolar disorder

High-Dose Ziprasidone
Patients with treatment-resistant psychosis may benefit from higher-than-recommended doses of ziprasidone (Geodon).

Baby Steps
Our clinical knowledge in psychiatry has increased over the past year, but scientific understanding and intervention technology still leaves much to be desired.

Index, Volume 30, 2007

High-Dose Ziprasidone

December 2007

One of the newer second-generation antipsychotics, ziprasidone (Geodon) carries a maximum recommended dosage of 160 mg/day. Evidence suggests that higher doses, at least up to 200 mg/day in clinical trials, bring greater efficacy.

Deutschman and Deutschman have prescribed ziprasidone for patients with treatment-resistant psychosis at doses higher than those approved by the US Food and Drug Administration.1 They report on a retrospective chart review of the safety and efficacy of this open-label clinical practice.

In the authors' community general hospital, patients are offered an opportunity for higher doses of ziprasidone if they have a partial response during 6 to 12 months of ziprasidone treatment at up to 160 mg/day, are free from side effects, and give consent for "off-label" dosing. The authors identified 106 records of patients with schizophrenia or affective spectrum disorders treated with ziprasidone, 180 to 640 mg/day, in inpatient or outpatient settings. Patients in the survey had taken high ziprasidone doses for less than 1 month to more than 2 years. In general, the higher doses brought a greater improvement in psychotic symptoms than patients had experienced at standard doses.

About three-quarters of the patients experienced no adverse events at the higher doses. Only two discontinued ziprasidone because of adverse effects: restless legs in one, and akathisia in the other. The most common adverse events were sedation, extrapyramidal signs, and other central nervous system events. No patient had significant weight gain. Higher ziprasidone doses did not appear to prolong the QT interval.

Obviously, these retrospective open clinical data must be treated as preliminary. However, patients who fit the profile described by Deutschman and Deutschman might be considered for high, off-label doses of ziprasidone. When high doses are employed, it is wise to monitor the electrocardiogram.

1Deutschman DA, Deutschman DH: High-dose ziprasidone in treatment-resistant schizophrenia and affective spectrum disorders: A case series. J Clin Psychopharmacol 2007;27:513-514.