Haematological safety of antipsychotic drugs

Abstract

Many clinicians have become concerned about the safety of new antipsychotics particularly in view of the association of agranulocytosis with clozapine and of aplastic anaemia with remoxipride. The Committee on Safety of Medicines and Medicines Control Agency 'yellow card' post-marketing surveillance data were analysed for reports of haemopoietic disorders with the 16 antipsychotics in common use. Corrections for relative risk were made in three separate ways: (i) control for degree of use, using Northern Ireland prescribing data for 1995; (ii) percentage of total reports from 1963 to 1996; and (iii) examination of the first 5 years' post-marketing data only. After clozapine and remoxipride the highest risks of haemopoietic reactions appeared to be associated with the aliphatic phenothiazine derivatives thioridazine and chlorpromazine. There is therefore no evidence of any increased risk with high-potency drugs such as haloperidol or pimozide or with the newer drugs such as sulpiride or risperidone. Continued vigilance, however, is necessary as more new atypicals become available and begin to be widely prescribed.

Where to Position Clozapine: Re-Examining the Evidence

“…By this point, mortality rates are comparable with the risk of developing these side effects with other nonrestricted antipsychotics. For example, it has been reported that chlorpromazine's risk of agranulocytosis is 0.13%, 45 while a recent study estimated the risk for olanzapine in this regard to be 0.15%. 46,47 In summary, clozapine registries and their associated compulsory blood monitoring systems (no blood, no drug) have established their effectiveness in reducing both the incidence of clozapine-induced agranulocytosis and associated mortality rates.…”

Haematological toxicity of drugs used in psychiatry

“…The ability of new drugs to cause a rare dyscrasia often does not become apparent until the drug is used more widely after licensing, hence such reactions may only be identified during post-marketing studies or after widespread use of the compound (King and Wager, 1998). Clinicians managing a blood dyscrasia should always bear in mind the possibility that it may be drug-induced (Bhatt and Saleem, 2004).…”

“…The risk is highest for both neutropenia and agranulocytosis within the first 6-18 weeks of treatment and most cases occur within the first 6 months (Atkin et al, 1996)-the risk of developing agranulocytosis falls to 0.08% after 1 year of treatment, that is after 1 year the risk is similar to that with chlorpromazine (chlorpromazine agranulocytosis risk up to 0.13%; King and Wager, 1998). The mortality rate due to clozapine-induced agranulocytosis has been estimated at 3-4% of identified agranulocytosis cases (Gerson, 1994).…”

A systematic review of atypical antipsychotic drugs in schizophrenia

“…117,121,124 Ten studies related to the incidence of blood dyscrasias such as agranulocytosis and leucopenia. [125][126][127][128][129][130][131][132][133][134] One was a study of NMS, 135 another of venous thromboembolic complications that occurred during clozapine treatment. 136 Five were studies of epilepsy or seizure rates 122,[137][138][139][140] …”