Up to 70% of patients with schizophrenia do not achieve full remission, even when taking antipsychotic medi- cations as recommended and this often lead to use of combination antipsychotics.Clozapine remains the only proven treatment for patients who do not respond fully to other antipsychotics. Despite this, clozapine is under utilised . No randomized clinical trial has directly compared clozapine with combinations of anti- psychotics.
A recent study (Essock et al 2011) showed that patients on two antipsychotics can be weaned off one of them without increased symptoms or hospitalisation.Switching to mono therapy was beneficial in most.
Evidence base for options available in clozapine resistant cases is thin.Clozapine augmentation with aripiprazole was effective in positive symptoms but not in cognitive symptoms. Augmentation with duloxetine was also beneficial.
There are no proven treatments for negative symptoms. A meta-analysis showed a modest effect size of 0.48 in favour of using antidepressants, but this decreased to 0.33 when three outlier results were dropped. A study from Finland showed that antidepressants can decrease mortality (beyond just decreasing suicide rates) suggesting that these agents might have some protective effects.
The most recent Cochrane systematic review do not find evidence that benzodiazepines are useful beyond short-term sedation in schizophrenia .Valproic acid is sometimes used to accelerate the response to antipsychotics . Although helpful in the acute situation, there is no demonstrated benefit to this strategy after 6 months. A meta analysis showed that Lamotrigine did not do better than placebo as a clozapine-augmentation strategy.Small studies indicate little benefit for topiramate as well.
When psychotropic combinations are tried in resistant cases clinicians often continue with the combination despite evidence of no benefit ( as long as there are no side effects) .It is true that many schizophrenia treatment decisions are not adequately informed by research. Polypharmacy approaches are often reasonable strategies, but should be undertaken with the knowledge that these are not evidence-based practices and close monitoring of benefit is essential.
Summary of the article:
Polypharmacy for schizophrenia. Ballon J, Stroup TS. Curr Opin Psychiatry. 2013 Mar;26(2):208-13.