[Effects of co-administration of an antidepressant and an anxiolytic drug in the "learned helplessness" paradigm: importance of hydroxyzine].
Whereas benzodiazepines are routinely coadministered with tricyclic antidepressants, in patients undergoing treatment for depressive disorders, little information is known about the combination of benzodiazepines with other antidepressants such as specific serotonin reuptake inhibitors (SSRI's), and combination with other anxiolytic drugs. On the other hand, it is known that benzodiazepines decrease the serotoninergic transmission. The present study was undertaken to evaluate the effect of concomittant administration of anxiolytic drugs such as benzodiazepines (diazepam, lorazepam) or diphenylmethane derivative (hydroxyzine) with specific serotonin reuptake inhibitors, (fluvoxamine, fluoxetine, indalpine) on the ability of antidepressant drugs to reverse helpless behavior in this test. Our results show that: daily injection of diazepam (0.25-2 mg/kg), lorazepam (0.06-0.25 mg/kg) or hydroxyzine (8.32 mg/kg) failed to reverse the behavioral deficit in rat. In contrast fluvoxamine: 4 mg/kg/day; fluoxetine: 4 mg/kg/day; indalpine: 1 mg/kg/day significantly reverse the helpless behavior in this test; the reversal of helpless behavior by fluvoxamine or indalpine was dose-dependently antagonized by daily coadministration of diazepam or lorazepam; in contrast, the reversal of helpless behavior by fluvoxamine or fluoxetine was not modified by daily coadministration of hydroxyzine (8 mg/kg). In conclusion, it may be suggested that combined benzodiazepine-specific serotonin reuptake inhibitors, should be avoided. We suggest that anxiolytic drugs such as hydroxyzine might be better in coadministration with antidepressants, particularly with specific serotonin reuptake inhibitors.
Martin
P
P
AMC Research Group, Paris.
Guillou
N
N
Lacroix
P
P
Billardon
M
M
D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D018687:Antidepressive Agents, Second-Generation / Q000494:pharmacology*; D001569:Benzodiazepines; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D006380:Helplessness, Learned; D006919:Hydroxyzine / Q000494:pharmacology*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology*
D014151:Anti-Anxiety Agents; D018687:Antidepressive Agents, Second-Generation; D001569:Benzodiazepines; D006919:Hydroxyzine; D017367:Selective Serotonin Reuptake Inhibitors