Olanzapine: concordant response in monozygotic twins with schizophrenia
I. Mata, V. Madoz, M.J. Arranz, P. Sham, R. M. Murray

There is growing evidence that genetic variation in several neurotransmitter systems (e.g. serotonergic) may influence the clinical response to different psychopharmacological drugs (Arranz et al, 1998, 2000). A previous paper (Vojvoda et al, 1996) described the concordant clinical response of a pair of monozygotic twins with schizophrenia when treated with clozapine. Now we report on two monozygotic twins concordant for DSM-IV (American Psychiatric Association, 1994) schizophrenia whose clinical response to olanzapine was also concordant.

The twins are now 60 years old. Twin 1 developed her first psychotic symptoms at age 21. Since then, she has been repeatedly admitted to hospital because of worsening of her psychotic symptoms, never returning to her premorbid level of functioning. She was treated with a wide variety of conventional antipsychotics, always with a poor response. Prior to her first psychotic break-down, she suffered a seizure, and was treated with phenobarbital and valproate. At age 58 years she was started on olanzapine building up to a high dose (20 mg daily) to control her symptoms. With this drug she had a good response (both in positive and negative psychotic symptoms) and an improvement in her level of functioning.

Twin 2 had her first psychotic episode and hospital admission at age 24. Subsequently, she was treated with different conventional antipsychotics as well as with clozapine, but never achieved a successful recovery. She needed several hospital treatments and suffered two seizures, with normal electroencephalogram while taking clozapine and levomepromazine, and agranulocytosis under clozapine treatment. Encouraged by her sister's response to olanzapine, she was treated with 20 mg olanzapine daily. She showed a good response, soon improving in both positive and negative symptoms, and in her level of functioning. Each twin is now symptomfree, working and living unaided. Their response to olanzapine treatment has been similar both in intensity and in the pattern of symptoms that have improved. To our knowledge, this is the first report describing monozygotic twins with similar illness characteristics who showed a similar response to olanzapine treatment. Our finding supports the view that, as with clozapine, genetic factors may be important in predicting response to olanzapine and other antipsychotic drugs.