Impulse regulation disorders and
substance abuse disorders have considerable consequences for treatment and prognosis of comorbid
psychiatric disorders. Second generation
antipsychotics (SGA) are frequently prescribed off-label for these disorders. This
off label use of SGA entails some systematic problems, such as lack of knowledge about their long-term efficacy and effects, including side-effects, and unclarity about doses in certain disorders and patient groups, for example children and adolescents. In this review we describe the evidence that supports
off-label use of the second generation
antipsychotics risperidone,
olanzapine,
clozapine,
ziprasidone,
quetiapine and
aripiprazole in impulse regulation disorders and
substance abuse disorders. We discuss these disorders together since we argue that the central feature of impulsivity in both disorders is a possible target for
antipsychotic medication. Subsequently we discuss the adverse effects of these agents and we consider some hypotheses about the mechanism of action in these disorders. Several double-blind randomised placebo-controlled trials have proven that
risperidone is effective in
attention-deficit and disruptive behavior disorders in children and adolescents, in behavioral problems and subaverage intelligence and in
tic disorders. Some double-blind randomised placebo-controlled trials, open-label studies and case reports find efficacy of
olanzapine in
tic disorders and pervasive developmental disorder.
Risperidone and
olanzapine are found to be ineffective in
substance use disorders. In
tic disorders two double-blind randomised placebo-controlled trials show inefficacy of
clozapine and efficacy of
ziprasidone. Some open-label studies found no benefit of
quetiapine in pervasive developmental disorder. Single-blind and open-label studies argue the benefit of
clozapine,
quetiapine and
aripiprazole in
substance abuse and dependence. A few open-label studies and case reports suggest efficacy of
quetiapine,
aripiprazole and
ziprasidone in
attention-deficit and disruptive behavior disorders in children and adolescents and in
tic disorders. Metabolic side effects such as hyperglycaemia and
diabetes mellitus,
weight gain and hyperlipidaemia are reported in all SGA, but especially in
clozapine and
olanzapine. In children they seem to be more pronounced than in adults. The most reported side effect in off-label SGA use in children, adolescents and adults is sedation. More double-blind randomised placebo-controlled trials into the long-term efficacy and safety of second generation
antipsychotics are needed. Moreover head to head comparison of SGA against each other and against first-generation
antipsychotic medication is still needed to determine the superiority of specific agents in treatment of specific disorders.