ABSTRACT
Several studies indicate an association between human leukocyte antigens (HLA) and clozapine-induced agranulocytosis. The authors have previously reported a significantly increased frequency of HLA-A1 among patients with schizophrenia who do not respond to conventional drugs, but do respond to clozapine treatment. In this study, the authors addressed the question of whether the same association is found in patients developing granulocytopenia or agranulocytosis. The frequency of the HLA-A1 allele in patients with clozapine-induced agranulocytosis or granulocytopenia was low (11.5%), whereas HLA-A1 was associated with a good therapeutic response to clozapine at an allele frequency of 58%. The frequency of HLA-A1 is 20% in the Finnish population. These results suggest that HLA-A1 may predict a good therapeutic outcome and a low risk of agranulocytosis and, thus, enable defining a subgroup of patients with schizophrenia in whom clozapine treatment could be started early to stop the disease from progressing.
Subject(s)
Agranulocytosis/genetics , Antipsychotic Agents/therapeutic use , Clozapine/therapeutic use , HLA-A1 Antigen/genetics , Schizophrenia/genetics , Adult , Aged , Agranulocytosis/chemically induced , Antipsychotic Agents/adverse effects , Clozapine/adverse effects , Female , Gene Frequency , Genetic Predisposition to Disease , Humans , Male , Middle Aged , Prognosis , Risk Factors , Schizophrenia/complications , Schizophrenia/drug therapyABSTRACT
BACKGROUND: It has not been investigated whether thyroid augmentation should precede lithium augmentation or vice versa. METHODS: In 22 outpatients with major depression not responsive to 4 weeks of antidepressant treatment, the effect of subsequent 4 weeks of thyroxine administration followed by 4 weeks of lithium augmentation was compared with the effect of the same treatments in reverse order. RESULTS: The percentage reduction in MADRS score was significantly greater in patients who started on thyroxine. CONCLUSIONS: Thyroxine augmentation should precede lithium augmentation. LIMITATIONS: We used relatively small doses of lithium. CLINICAL RELEVANCE: Thyroxine is effective in augmenting antidepressant responses.
Subject(s)
Antidepressive Agents/administration & dosage , Depressive Disorder/drug therapy , Lithium/administration & dosage , Thyroxine/administration & dosage , Adolescent , Adult , Antidepressive Agents/pharmacology , Antidepressive Agents/therapeutic use , Drug Administration Schedule , Drug Synergism , Drug Therapy, Combination , Female , Humans , Lithium/pharmacology , Lithium/therapeutic use , Male , Pilot Projects , Thyroxine/pharmacology , Thyroxine/therapeutic use , Treatment OutcomeABSTRACT
We report an association between HLA-A1 allele and a subgroup of schizophrenic patients refractory to conventional neuroleptic treatment but responsive to clozapine. The frequency of HLA-A1 was 58% among the schizophrenic patients not responding to conventional treatment but responsive to clozapine but only 10.5% among the patients responding to conventional neuroleptics. The HLA-A1 occurs in 20% of the random Finnish population. Our results indicate that HLA-A1 defines a subgroup of schizophrenic patients with a selective response to neuroleptics.
