Anxiety and aggressive outbursts under long-acting injectable risperidone (RISPERDAL CONSTA): Unlike conventional long-acting injectable neuroleptics such as haloperidol decanoate (e.g. HALDOL DECANOATE) depot risperidone (RISPERDAL CONSTA) is available micro-encapsulated in a copolymer of lactic and glycolic acid. It is injected every two weeks. However, the active substance is only released significantly from the third week on (initially less than 1%). Therefore patients must continue to take their oral dose in the first three weeks. Constant plasma levels are not reached until after the fourth injection. This complicates dose escalation when needed (at the earliest after four weeks in any case) and dealing with forgotten or delayed injections. A consultant psychiatrist reports on two female schizophrenic patients, in their mid fifties and sixties respectively, in whom there was a sudden onset of restlessness, agitation, akathisia, anxiety, feelings of tension and aggressive outbursts, after three or four injections of depot risperidone. She presumes that "the drug may be released differently in individual cases and occasionally abrupt high concentrations may be delivered, thus leading to undesired, very agonizing side effects". Because of the three-week latency period until the substance is released she fears that owing to premature dose increases "patients will be given an overdose on the assumption that the dose is still not sufficient" (NETZWERK reports 13.170, 13.171). On the other hand, lack of efficacy of the long-acting preparation may be blamed as a possible cause. After evaluating two studies, in which the depot neuroleptic was compared with placebo and risperidone tablets, the authors of a COCHRANE review concluded that there "is no reliable data to support the claim that depot risperidone is beneficial for people with schizophrenia." With 56% of subjects interrupting the study, it is difficult to imagine that the drug improves compliance (HOSALLI, P., DAVIS, J.M. Depot risperidone for schizophrenia [Cochrane Review]. In: The COCHRANE Library, Issue 1, 2004, Chichester, UK: John WILEY & Son, Ltd.). Extrapyramidal motor symptoms occur frequently with higher dosages of the depot preparation (50 mg [= official maximum dose] and 75 mg), at 24% and 29%, and require additional anticholinergic treatment in almost one out of four patients (KANE, J.M. et al.: Am. J. Psychiatry 2003; 160: 1125-32). Long-term data on depot risperidone from controlled randomised studies are lacking.