Abstract
Antipsychotic treatment of schizophrenia is, to borrow from Winston Churchill, a riddle, wrapped in a mystery, inside an enigma. There is so much we do not understand. Why should drugs with almost identical modes of action afford such varied effects in individuals but appear more or less uniformly effective in populations? Why do antipsychotics lose their effectiveness in some people, despite full adherence? Why does almost everyone relapse on cessation of antipsychotics but not quite everyone?
Another aspect of the riddle is the question of prescriber attitudes to prescribing different drugs alone or in combination. Why wait to prescribe clozapine when it is by far the most efficacious drug? One reason frequently cited is that prospective patients refuse to accept clozapine and would not take it, especially after discharge. This is probably not true, as demonstrated by Inti Qurashi and colleagues in their study reported in this issue. A total of 56 male forensic patients gave their personal views of clozapine treatment. A massive majority (86%) reported that clozapine was better than previous treatments and not one thought it worse. A majority also reported improvements in quality of life and social interaction. On the negative side, almost all subjects described nocturnal hypersalivation as a troublesome adverse effect.
Despite clozapine’s efficacy advantages its adverse effect profile is problematic, to say the least. So if not clozapine, then which better-tolerated antipsychotic should we choose? In this issue Saeed Shafti and Hamid Kaviani describe their comparison of quetiapine and aripiprazole in nonrefractory schizophrenia. The effect of the drugs was essentially identical in respect to efficacy. On the one hand this is to be expected: we are used to finding that nonclozapine antipsychotics to have broadly equal efficacy. On the other, why should a weak dopamine antagonist produce the same clinical outcomes as a high-affinity dopamine partial agonist?
Of course, our choices are not limited to a range of drugs but also a range of formulations of antipsychotics. One might expect the continuous parenteral delivery of antipsychotic to have distinct advantages over the potentially erratic delivery from oral medication. However, randomized controlled trials rarely show this to be the case. In this issue, Paul Deslandes and colleagues report on their observational study of naturalistic use of risperidone long-acting injection (RLAI) and oral aripiprazole. There were few important differences: continuation rates of 5 years were 18% for RLAI and 16% for oral aripiprazole. Again we are reminded of a well-known but unexplained feature of antipsychotic treatment: very few people stay on the same drug for any length of time.
While most antipsychotics block dopamine, most illicitly misused substances enhance dopaminergic function in some way. George Awad and Lakshmi Voruganti, in this issue, review the literature pertaining to the close association between substance misuse and (the treatment of) schizophrenia and came to a remarkable conclusion. It is this: even low-level central dopamine antagonism can lead to a dysphoric state; those individuals who suffer dysphoria are precisely those who seek out illicit substances and use them to reverse the dysphoria.
Two further papers in this issue deal with the treatment of depression. In one Rachel Patel and Daniel Titheradge examine the evidence supporting MDMA in mood disorders and find it to be flimsy, at best. In the second, Ravindran and coworkers describe their analysis of real-life prescription data for antidepressants and their effect on weight. All antidepressants studied increased weight with the exception of bupropion, but adding bupropion to escitalopram gave rise to greater weight gain than escitalopram alone. Clearly a great deal of further work is need to be done in this area and the other areas of psychopharmacology touched on in this issue.