137 - Treatment first steps

Treatment – first steps

Schizophrenia and related psychoses CHAPTER 1 Treatment of tardive dyskinesia Tardive dyskinesia is a somewhat less commonly encountered problem now than in previous decades,1,2 probably because of the more widespread use of SGAs,3–6 which generally have a lower risk for the condition than FGAs. Treatment of established TD is often unsuccessful, so prevention, early detection and early remedial action are essential.7,8 There is evidence to suggest that TD is associated with greater cognitive impairment,7,9 more severe psychopathology10,11 and higher mortality.12,13 While the majority of patients seem to be unaware of the involuntary movements, the condition can still impose a substantial burden on physical, psychological and social well-­being.14–16 While SGAs are less likely to cause TD,17–23 the condition still occurs with these medications. An extensive meta-­analysis of relevant studies found the annualised incidence of TD across all FGA treatment groups was 6.5%, while the respective figure for SGA treatment groups was 2.6%.24 However, there is a significant variation in liability between individual SGA medications.24–28 The risk of developing TD may be related to the extent of D2 receptor occupancy (greater occupancy, higher risk) with a medication,29 although data from the meta-­analysis mentioned above did not support the notion that the lower risk of TD with SGAs is a consequence of the use of relatively high equivalent doses of FGAs.24 There is a hint that dopamine partial agonists (or, at least, aripiprazole) may have the lowest liability for TD.24 Whether the risk of TD differs between LAI FGA and LAI SGA preparations is unclear30 but there is one report suggesting that the risk of TD with LAI SGAs is lower than with the equivalent oral SGA preparations.31 TD can occur even with low doses of haloperidol (and in the absence of prior acute movement disorder)32 and with the use of other dopamine antagonists such as metoclopramide.33 The characteristic abnormal involuntary movements of TD have also been observed in never-­medicated patients with both first-­episode34,35 and established36 schizophrenia. This suggests that the use of antipsychotic medication adds to an inherent risk of TD that is present in people with a diagnosis of schizophrenia. Treatment – first steps Most authorities recommend the withdrawal of any co-­prescribed anticholinergic agents and a reduction in the dose of antipsychotic medication (which may initially worsen TD) as initial steps in those with early signs of TD,37,38 although there is a lack of robust evidence to support such a strategy.14,39–41 Nevertheless, it is common practice to withdraw the antipsychotic prescribed when TD is first observed and to substitute it with an antipsychotic medication that is perceived to have a lower liability for the condition. However, the evidence for a beneficial effect on TD when switching to any particular SGA is limited.42 Changing to clozapine37,43 is probably best supported,37,43–45 but quetiapine, another weak striatal dopamine antagonist, may also be effective.46–52 Olanzapine39–42,53,54 and aripiprazole55 are also potential options.