Сравнение атипичных антипсихотиков

For example, when switching from a tightly binding anticholinergic or antihistaminergic medication (eg, olanzapine, quetiapine, clozapine) to one with less anticholinergic or antihistaminergic affinity (eg, aripiprazole, risperidone, ziprasidone), often transient rebound anxiety, insomnia, agitation and restlessness can occur. In addition, when switching from a tighter D2 binding agent to a looser-binding agent (eg, from risperidone to clozapine or quetiapine) or, particularly, to a partial dopamine agonist (eg aripiprazole) dopamine rebound symptoms, such as often transient worsening of psychosis, mania or aggression/agitation, can occur. A pharmacokinetic dopamine rebound may also occur when switching from a short half-life antipsychotic to a longer half-life antipsychotic (Table 1).4

The abrupt switch has the greatest potential for rebound and withdrawal phenomena. Even the conventional cross-titration can lead to problems when the pre-switch antipsychotic has a shorter half life and/or blocks more tightly cholinergic, histaminergic or dopaminergic receptors than the post-switch antipsychotic. Rebound phenomena can be minimized by avoiding abrupt or fast switching when the pre- and post-switch receptor affinities and/or half-lives differ considerably. Instead, an overlapping or “plateau” switch should be used. This consists of decreasing the pre-switch antipsychotic slowly (eg, 25–50% every 5 half-lives) and only after the post-switch antipsychotic has reached steady state (ie, ≤5 half lives on target dose). Adding calming medications during the switch period, such as benzodiazepines, antihistamines or sleep aides, can also minimize rebound phenomena.

A number of non-antipsychotic augmentation strategies have also been tested in schizophrenia patients with insufficient response to antipsychotic monotherapy. Of these, lithium,16 carbamazepine,17 and beta blockers18 were not superior to placebo when added to an antipsychotic. Similarly, benzodiazepine19 and valproate augmentation20 also did not show long-term superiority compared to placebo, although both agents might speed up the initial response. Although two large-scale studies showed no superiority of lamotrigine augmentation of antipsychotics compared to placebo,21 a meta-analysis demonstrated significant superiority regarding global ratings of psychopathology, positive and negative symptom change, as well as study-defined response when outcomes of patients were combined in whom lamotrigine was added to clozapine.22 This, however, has not been verified in a prospective study.

ECT augmentation has also been shown to be superior, both for acute efficacy and in maintenance treatment, when added to antipsychotic monotherapy in patients who have failed antipsychotic monotherapy.23

One meta-analysis suggested that augmentation of antipsychotics with antidepressants may be more helpful than placebo for schizophrenia patients with predominantly negative symptoms.24 Larger, validating studies are needed, however, and specific effects on negative symptoms need to be distinguished from proven effects of antidepressants on depressive symptoms in schizophrenia patients.25

Practical Dosing Strategies in the Treatment of Schizophrenia: Part 2 - Switching and Combining Antipsychotics