Refractory schizophrenia poses many therapeutic dilemmas.
Clozapine is currently considered as the most effective medication for the treatment of
refractory schizophrenia. Unfortunately, it carries serious and often life-threatening adverse effects such as agranulocitosis,
hypersalivation,
somnolence,
weight gain, diabetes, and epileptic
seizures. Various combinations of
clozapine with typical and other atypical
antipsychotics have been suggested to improve its efficacy and reduce its often dose-related adverse effects. We present a case of a 37-year-old patient with
refractory schizophrenia who has responded well to the combination of
clozapine,
sodium valproate, and
pipamperone. The improvement was more evident in the following symptoms:
auditory hallucinations, delusions, formal thought disorder,
anhedonia, and social withdrawal. The combination was well tolerated: No extrapyramidal adverse effects were noted and the patient's full blood count was within normal limits.
Pipamperone, a butyrophenone derivative, is a more selective antagonist of dopaminergic D4 receptors compared with D2 receptors and a serotoninergic 5HT-2A receptors antagonist. Thus, it shows "atypicality" and shares common characteristics with
clozapine: 5HT-2A antagonism and D4 > D2 blockade selectivity. Therefore, augmentation of
clozapine with
pipamperone theoretically should have a synergistic effect that may provide several benefits to the patient: better
antipsychotic efficacy with low risk for extrapyramidal adverse effects. This combination may also allow a decrease in
clozapine dose, limiting its challenging adverse effects. To the author's knowledge, successful treatment of
refractory schizophrenia with this
drug combination is reported for the first time in the literature and probably merits further research.