You would like to add a second antipsychotic. The options addressed here are to combine two standard typical neuroleptics, to combine two atypical antipsychotics (other than clozapine), or to combine a standard typical with an atypical. If you plan to start (or the patient already is taking) clozapine (with or without other antipsychotics), go back and choose the clozapine option in the last question.
Many patients are treated with more than one antipsychotic at a time, a practice sometimes referred-to as antipsychotic polypharmacy. This has received little study.(1) Virtually all practice guidelines and evidence-based algorithms advocate sequential monotherapies of two (or more) atypical and typical antipsychotics followed by monotherapy with clozapine, and that is the basic approach recommended in this interactive algorithm. In the absence of data, the potential disadvantage of polypharmacy is that side effects, including inhibition of some benefits, will outweigh any advantages.(2) One study found that patients on two or more antipsychotics were significantly more likely to die over a 10 year period.(3) However, this matter is badly in need of study. Yet, this is unlikely to occur in the near future: this will remain a murky practice area where many clinicians are deviating from what experts recommend, yet we do not know if the experts are right or whether clinicians have discovered something.
Combining typical with atypical agents may have some theoretical advantages.(2) Surveys suggest combinations are used more commonly when olanzapine or quetiapine is one of the antipsychotics.(4) There are some clinical reports suggesting that this combination is helpful, but they were unclear as to the adequacy of previous monotherapy trials, and assessment validity and investigator bias may be questioned. Also, pharmacokinetic effects could have explained the apparent pharmacodynamic synergism.(2) No controlled studies exist to justify this frequently-used combination.
Combining two typicals used to occur often in the era prior to the introduction of the atypicals, and still does occur in many parts of the world. Yet, no systematic data support this practice. Any theoretical advantages involving balancing side effects could be addressed more appropriately with atypicals. However, there may be some sites where funding or other factors makes it impossible to obtain atypicals. Even then, the same proposed benefits are more likely to be obtained by other mechanisms, such as by adding anticholinergics, mood stabilizers, or anxiolytics.(2)
Combining two (non-clozapine) atypicals is a very expensive practice, and like the other combinations does not enjoy any evidence-basis. There might be some theoretical advantage to a combination like quetiapine and risperidone (strong D2 effect in the latter combined with rapid release from D2 in the former). But, the risperidone in this equation could be replaced at much lower cost by low-dose haloperidol.
In summary, if the other choices of actions to take, presented in the question that brought you to this discussion, are not appropriate or have been tried, the option of polypharmacy with antipsychotics exists. The most rational combination appears to be a combination of a typical and an atypical. {Scroll past the references to find the Recommendation Number and access the Data Reporting Form}
(1)Stahl SM. Antipsychotic polypharmacy. Part 1: Therapeutic option or dirty little secret? J Clin Psychiatry 1999;60(7):425-426
(2)Meltzer HY, Kostakogly E. Combining antipsychotics: is there evidence for efficacy? Psychiatric Times 2000;10(9):25-34.
(3)Waddington JL, Youssef HA, Kinsella A. Mortality in schizophrenia: antipsychotic polypharmacy and absence of adjunctive anticholinergics over the course of a 10 year prospective study. Br J Psychiatry 1998;173:325-329.
Recommendation #156
