Imipramine

Orthostatic laypoteasloa: eompar". "lth aortrl,tyllae While the development of orthostatic hypotension with imipramine has been well documented. there is disagreement over the orthostatic effect of nortriptyline. 67 patients with severe depression requiring hospitalisation were studied: 44 on imipramine were studied in a previous trial; I S on nortriptyline were seen by a psychiatrist over a 3-year period; and 8 patients were treated consecutively with imipramine and nortriptyline. Some of the patients in the crossover comparison had beeD unable to toIerat6 imipramine because of C)rthbstatic hypotelaicm. The mean orthostatic drop on nortriptyline increased from a pre-c1rug level of 8mm HI to J Imm Hi (p < 0.001). Witb jrrtipraminetbe mean orthostatic drop increased from Ilmm Hi (pre-drua) to 26mm Hi (p < 0.00 r). AnaJysis of covariance in the crossover IXIMparisoD showed. a peater orthostatic drop on imipramine tbaIl OD

IlOrtriptyline(p< 0.001). A pUed t-te&t showed a statisticaUy sianirlCl.Dt increase in orthostatic drop with imiPramine IXImpared with nortriptyline. Some patients who repeatedly fell or fainted when standing with imipramine bad no p~Jems with nortriptyline. The finding that nortriptyline has a significantly reduced orthostatic effect oompared with imipramine should help the doctor to reduce the risk in his most vulnerable patients. It has been suggested that tricyc1ics exert this effect by ctl-adrenergic blockade but this does not seem to be supported by clinical evidence as nortriptyline and imipramine bave equivalent Cll-adreneraic bIock.illl effects. both havilll a greater effect than desmethylimipramine. Clz-Blockade and L-gluCamate may also be involved but the mechanism is complel( and. as yet. undetermined. ROOI!Ie. s.P. et al.: Journal orOiJIiaIJ Psyl:bopharmllaJloty I: 316 (SIp 1981 )

0157-7271/82/0129-0005/0$00.50/0 CADIS Press Reactions 29 Jilin 1982 5