Addition of low-dose fluvoxamine to low-dose clozapine monotherapy in schizophrenia: drug monitoring and tolerability data from a prospective clinical trial.
Combining fluvoxamine and clozapine may be a strategy to improve therapeutic effects on negative symptoms in schizophrenic patients. Fluvoxamine, however, markedly inhibits the metabolism of clozapine, and hazardous side effects may result. This study prospectively investigated the safety and tolerability of an add-on therapy with fluvoxamine to a clozapine monotherapy in schizophrenic patients. Sixteen schizophrenic patients received 50 mg fluvoxamine as a comedication after having reached steady-state conditions under clozapine monotherapy. Patients were monitored for subjective adverse events, laboratory parameters, EEG and ECG recordings, orthostatic hypotension and their psychopathology. Concomitantly, serum concentrations of clozapine and metabolites were measured during monotherapy and after addition of fluvoxamine. In all patients, the serum concentrations of clozapine and metabolites were markedly increased (average: 2-3 fold, up to 5 fold for clozapine) after addition of fluvoxamine. Side effects remained almost unchanged in frequency and severity in spite of the pharmacokinetic interactions. ECG or laboratory parameters and orthostatic tests were similar under monotherapy and comedication. Minimal increases of EEG abnormalities were observed, but they were not associated with clinical impairment. Epileptic activities were always absent. The psychopathology improved which continued after start of the comedication. Though the addition of fluvoxamine to clozapine medication was well tolerated and critical side effects were absent, the combined treatment should be controlled by drug monitoring, as serum concentrations of clozapine increased to unpredictably high levels. Further studies have to find out if the combined treatment could be advantageous to clozapine monotherapy.
Szegedi
A
A
Department of Psychiatry, University of Mainz, Germany. szegedi@mail.psychiatrie.klinik.uni-mainz.de
Anghelescu
I
I
Wiesner
J
J
Schlegel
S
S
Weigmann
H
H
Härtter
S
S
Hiemke
C
C
Wetzel
H
H
D000293:Adolescent; D000328:Adult; D018687:Antidepressive Agents, Second-Generation / Q000008:administration & dosage / Q000627:therapeutic use*; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D003024:Clozapine / Q000627:therapeutic use*; D004334:Drug Administration Schedule; D004347:Drug Interactions; D016903:Drug Monitoring; D004359:Drug Therapy, Combination; D005260:Female; D016666:Fluvoxamine / Q000008:administration & dosage / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D016555:Matched-Pair Analysis; D008875:Middle Aged; D011446:Prospective Studies; D012559:Schizophrenia / Q000188:drug therapy*; D017367:Selective Serotonin Reuptake Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D016896:Treatment Outcome
D018687:Antidepressive Agents, Second-Generation; D014150:Antipsychotic Agents; D003024:Clozapine; D016666:Fluvoxamine; D017367:Selective Serotonin Reuptake Inhibitors