The search for new off-label indications for antidepressant, antianxiety, antipsychotic and anticonvulsant drugs

The search for new off-label indications for antidepressant, antianxiety, antipsychotic and anticonvulsant drugs

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J Psychiatry Neurosci 2006;31(3):168-76

Guy Chouinard, MD

Fernand-Seguin Research Centre, Louis-H. Lafontaine Hospital; Department of Psychiatry, Université de Montréal; Clinical Psychopharmacology Unit, Allan Memorial Institute, McGill University Health Centre; and Department of Psychiatry, McGill University, Montréal, Que.

2004 CCNP Heinz Lehmann Award Paper: Part I

Abstract

Most drugs are prescribed for several illnesses, but it took several years for psychotropic drugs to have multiple clinical indications. Our search for serotonergic drugs in affective illnesses and related disorders led to new off-label indications for fluoxetine, sertraline, tryptophan, clonazepam, alprazolam, tomoxetine, buproprion, duloxetine, risperidone and gabapentin. Various clinical trial designs were used for these proof-of-concept studies. Novel therapeutic uses of benzodiazepines, such as in panic disorder and mania, were found with the introduction of 2 high-potency benzodiazepines, clonazepam and alprazolam, which were thought to have serotonergic properties. Our initial clinical trials of fluoxetine and sertraline led to their approved indications in the treatment of obsessive–compulsive disorder, and our trials of gabapentin led to new indications in anxiety disorders (generalized anxiety, panic attack and social phobia) and sleep disorders (insomnia).

Résumé

La plupart des médicaments sont prescrits pour plusieurs maladies, mais il a fallu plusieurs années pour que les psychotropes aient de multiples indications cliniques. Notre recherche de médicaments sérotoninergiques contre des maladies affectives et des troubles connexes est à l’origine de nouveaux emplois non conformes des médicaments suivants : fluoxétine, sertraline, tryptophan, clonazépam, alprazolam, tomoxétine, buproprion, duloxétine, rispéridone et gabapentine. On a utilisé divers concepts d’essais cliniques pour ces études de validation du principe. On a trouvé de nouvelles utilisations thérapeutiques pour les benzodiazépines, comme dans des cas de trouble panique et de manie, avec l’arrivée sur le marché de deux benzodiazépines de haute puissance, le clonazépam et l’alprazolam, qui semblaient avoir des propriétés sérotoninergiques. Nos premières études cliniques sur la fluoxétine et la sertraline ont débouché sur l’approbation de leurs indications dans le traitement du trouble obsessif compulsif, et nos études sur la gabapentine sont à l’origine de nouvelles indications contre les troubles de l’anxiété (anxiété généralisée, crise de panique et phobie sociale) et du sommeil (insomnie).


Medical subject headings: anticonvulsants; antidepressive agents; antipsychotic agents; anti-anxiety agents; depressive disorder, major; off-label indications; schizophrenia.

Competing interests: Dr. Chouinard has acted as a consultant for Solvay, Organon, Pfizer, Schering-Plough and Neuro3d.

Submitted Sept. 30, 2005; Revised Dec. 22, 2005; Accepted Jan. 10, 2006

Correspondence to: Dr. Guy Chouinard, Clinical Psychopharmacology Unit, Allan Memorial Institute, MUHC, 1025 Pine Ave. W, Montréal QC H3A 1A1; fax 514 982-6620; va.chouinard@gmail.com