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Revista Brasileira de Psiquiatria

Print version ISSN 1516-4446On-line version ISSN 1809-452X

Rev. Bras. Psiquiatr. vol.28 no.4 São Paulo Dec. 2006 



Efficacy of milnacipran in treating anxiety symptoms in schizophrenic patients receiving clozapine: a case series study


Eficácia do milnaciprano para o tratamento de sintomas ansiosos em pacientes esquizofrênicos medicados com clozapina: uma série de casos



Dear Editor,

The prevalence of anxiety disorders in psychotic patients has been found to be from 43 to 45%.1 Such disorders are associated with an increased risk of dependence on, or abuse of, alcohol and other substances, a higher number of suicide attempts and an increased risk of psychotic symptom recurrence.2 Anxiety symptoms have a significant negative impact on the quality of life of schizophrenic patients, independently of the presence of depressive symptoms.3-4

The benefits of using antidepressants to treat anxiety symptoms have been demonstrated in the individuals with psychosis.3 However, the use of antidepressants may worsen the psychotic symptoms.5 Although there have been few clinical studies of the effects of milnacipran on anxiety, it has been reported to be efficacious in the treatment of depression in patients with schizophrenia spectrum disorders.5

Six outpatients (4 males, 2 females) diagnosed with schizophrenia according to the DSM-IV and intense anxiety symptoms, although not meeting the criteria for any DSM-IV anxiety disorder, were studied in order to determine the efficacy of milnacipran in reducing anxiety symptoms in this population. All patients were under treatment with clozapine for refractory schizophrenia.

The mean age of the subjects was 35 ± 5 years. The mean daily doses of clozapine and milnacipran were 700 mg and 100 mg, respectively. All subjects were submitted to blood workups as recommended for clozapine-treated patients. No hematologic abnormalities were found in this group.

The efficacy of milnacipran in reducing anxiety symptoms, as characterized according to the Hamilton Anxiety Scale (HAM-A), which was applied before treatment (T0), after 4 weeks of treatment (T4) and after 8 weeks of treatment (T8). The Brief Psychiatric Rating Scale (BPRS) was also applied at T0, T4 and T8 in order to evaluate possible worsening of schizophrenia symptoms due to treatment with the antidepressant. Comparisons between groups were made using paired Student's t-tests. Table 1 shows the demographic data for the patients treated with milnacipran, as well as variations between T0 HAM-A and BPRS scores and those obtained at T4 and T8. The mean HAM-A scores decreased significantly (p = 0.014) from T0 (32 ± 7) to T4 (27 ± 9), remaining stable between T4 and T8 (28 ± 10; p = 0.523). From T0 to T8, a trend toward decreasing HAM-A was found (p = 0.069). The mean BPRS score remained virtually unchanged (p = 0.087) from T0 (71 ± 18) to T4 (67 ± 21), from T4 to T8 (66 ± 24) (p = 0.884) and from T0 to T8 (p = 0.326). No patient reported adverse effects related to the treatment.

Clearly, the small size of our sample precludes generalization, and studies involving larger samples are needed to confirm these findings. However, our results suggest that milnacipran might be effective in reducing anxiety symptoms in the fourth week of use, and this effect might be maintained until the eighth week of use. In addition, the tolerability profile and the low potential for drug interactions presented by milnacipran could make it a very useful alternative for treating anxiety in patients using clozapine, without the risk of drug interactions and worsening psychotic symptoms.


Clarissa Severino Gama, Vanessa Cassina Zanatto, Felipe Picon, Maria Inês Lobato, Paulo Silva Belmonte-de-Abreu
Department of Psychiatry, Hospital de Clínicas de Porto Alegre (HCPA), Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre (RS), Brazil



1. Cosoff SJ, Hafner RJ. The prevalence of comorbid anxiety in schizophrenia, schizoaffective disorder and bipolar disorder. Aust N Z J Psychiatry. 1998;32(1)67-72.

2. Pallanti S, Quercioli L, Hollander E. Social anxiety in outpatients with schizophrenia: a relevant cause of disability. Am J Psychiatry. 2004;161(1):53-8.

3. Wetherell JL, Palmer BW, Thorp SR, Patterson TL, Golshan S, Jeste DV. Anxiety symptoms and quality of life in middle-aged and older outpatients with schizophrenia and schizoaffective disorder. J Clin Psychiatr. 2003;64(12):1476-82.

4. Braga RJ, Mendlowicz MV, Marrocos RP, Figueira IL. Anxiety disorders in outpatients with schizophrenia: prevalence and impact on the subjective quality of life. J Psychiatr Res. 2005;39(4):409-14.

5. Nakanishi S, Kunugi H, Takahashi T. Efficacy of milnacipran for depressive symptoms in schizophrenia spectrum disorders. Psychiatr Clin Neurosci. 2004;58(2):226-7.

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