title: Does selectivity matter?
abstract: An important aim of drug development has been to retain efficacy while reducing side effects and toxicity. It is now clear that selective serotonin reuptake inhibitors (SSRIs) are more effective than noradrenaline reuptake inhibitors (NARIs) in the treatment of obsessional compulsive disorder, and obsessional features in depression predict a responsivity to SSRIs. Furthermore, panic disorder and depression may be more responsive to SSRIs than NARIs. However, there is evidence that inhibition of both sites produces slightly greater efficacy and the addition of an NARI has been reported to potentiate the antidepressant effect of SSRIs. Tricyclic noradrenaline-serotonin uptake inhibitors have many other pharmacological properties, which probably relate to high rates of side effects and cardiotoxicity. Whether in practice these features reduce compliance or increase deaths from suicide is debatable, but it seems wrong to subject patients to burdensome side effects. Certainly, in overdose, older non-selective antidepressants are far more likely to kill than SSRIs. SSRIs have their own side effects, such as nausea and anorgasmia, due to their potency at the uptake site, but these are reversible and sometimes treatable. Clearly, selectivity for specific uptake sites matters for efficacy, and selectivity for uptake over other sites matters for tolerability and safety.
authors.affiliation: University Department of Psychiatry, Manchester Royal Infirmary, UK.
authors.forename: J F
authors.initials: JF
authors.lastname: Deakin
mesh_terms: D000928:Antidepressive Agents / Q000494:pharmacology*; D015283:Citalopram / Q000009:adverse effects* / Q000494:pharmacology* / Q000627:therapeutic use; D003866:Depressive Disorder / Q000188:drug therapy; D006801:Humans; D012701:Serotonin / Q000378:metabolism; D017367:Selective Serotonin Reuptake Inhibitors / Q000009:adverse effects* / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D000928:Antidepressive Agents; D015283:Citalopram; D012701:Serotonin; D017367:Selective Serotonin Reuptake Inhibitors