Clozapine dysfunction

Current sexual dysfunction or concerns about Aripiprazole, quetiapine, clozapine Olanzapine, ziprasidone... 

Despite the widespread use of neuroleptics in maintenance treatment of bipolar disorder, there have not been any systematic studies of their suitability for this role. Through clinical experience it has been widely accepted that neuroleptics are useful adjunctive treatments to lithium and related drugs. Treatment refractory patients frequently respond to atypical antipsychotics such as clozapine or risperidone. Such adverse effects as EPS, cognitive dysfunction and weight gain frequently limit the long-term use of classical neuroleptics. For this reason, the atypical neuroleptics such as olanzapine and risperidone should now be considered as alternatives for maintenance treatment. 

Olney JW, Farber NB. 1995. Glutamate receptor dysfunction and schizophrenia. Arch Gen Psychiatry 52 998-1007. Onali P, Olianas MC. 2007. N-desmethylclozapine, a major clozapine metabolite, acts as a selective and efficacious delta-opioid agonist at recombinant and native receptors. Neuropsychopharmacology 32 773-785. 

The frequency and course of sexual disturbances associated with clozapine have been studied in a prospective open study in 75 men and 25 women, mean age 29 years, and compared with the effects of haloperidol in 41 men and 12 women, mean age 26 years (200). There were no statistically significant differences between the patients taking haloperidol and those taking clozapine. During 1-6 weeks of treatment with clozapine, the most frequent sexual disturbances among women were diminished sexual desire (28%) and amenorrhea (12%), while among men they were diminished sexual desire (57%), erectile dysfunction (24%), orgasmic dysfunction (23%), ejaculatory dysfunction (21%), and increased sexual desire (15%). The mean daily doses were haloperidol 16 mg and clozapine 261 mg. 

The presentation of neuroleptic malignant syndrome with clozapine can be different from that associated with traditional neuroleptic drugs (SEDA-28, 66), and the authors of a recent report have pointed out the differential diagnosis with heat stroke, a medical emergency with the two cardinal features of raised core body temperature (40° C) and central nervous system dysfunction, which is fatal in up to 50% of cases (205). 

Clozapine and olanzapine are the most likely of the atypical agents to cause anticholinergic (anti-muscarinic) effects. They are more likely than other atypicals to cause weight gain (glucose tolerance may be impaired and should be monitored in susceptible individuals) and are second only to quetiapine in their sedative effects. Sexual dysfunction and skin problems are rare with atypical antipsychotics. Risperidone and amisulpride are as likely as classical antipsychotics to raise prolactin concentrations and cause galactorrhoea. 

The possibility of renal dysfunction as a rare adverse effect should be considered. The patient had a history of allergic reactions to lithium, carbamazepine, clozapine, haloperidol, and lamotrigine. 

Extrapyramidal (EP) dysfunction is least likely to occur with clozapine and olanzapine, which do not block D2A receptors but are strong antagonists at 5HT2 receptors. 

Clozapine +/- Blocks D2c and 5HT2 receptors, no S EP dysfunction or TDs, j agranulocytosis—requirement for j weekly blood test, weight gain j... 

A mild jaundice, typically occurring early in therapy, may be seen in some patients receiving chlorpromazine. Pruritus is rare. The reaction probably is a manifestation of hypersensitivity, because eosinophilia and eosinophilic infiltration of the liver occur. For uninterrupted drug therapy in a patient with neuroleptic-induced jaundice, it probably is safest to use low doses of a potent, dissimilar agent. Hepatic dysfunction with other antipsychotic agents is uncommon. Clozapine can cause potentially severe ileus and sialorrhea. 

This drug has a high affinity for 5-HT2 receptors in the brain and does not cause extrapyramidal dysfunction or hematotoxicity it is reported to improve both positive and negative symptoms of schizophrenia (A) Chlorpromazine Clozapine Fluphenazine Olanzapine Risperidone... 

Tricky Many of the newer antipsychotic drugs have a greater affinity for 5-HT, receptors than dopamine receptors. However, since clozapine is hematotoxic, the choice comes down to olanzapine and risperidone, both of which block 5-HT receptors. Although the risk appears to be low, risperidone is repotted to cause extrapyramidal dysfunction, including tardive dyskinesia. The answer is (D). 

---