Sex-related elevation in cortisol during chronic treatment with alprazolam associated with enhanced cognitive performance.
OBJECTIVE
There is evidence of more widespread use and abuse of benzodiazepines (BZPs) among elderly women. However, factors underlying this observation are poorly understood but could be related to more intense withdrawal reactions, which are a major risk factor for continued BZP use. We previously reported elevations in interdose morning plasma cortisol levels in healthy elderly individuals after chronic treatment with alprazolam, possibly consistent with increased hypothalamic-pituitary-adrenal (HPA) axis activity and drug withdrawal. In this study, we examined sex-related differences in this population.


METHODS
Twenty-five cognitively intact healthy elderly (13 women and 12 men) participated in a parallel, double-blind, placebo-controlled study that included a group that received acute and chronic (3 weeks) treatment with alprazolam (0.5 mg b.i.d.).


RESULTS
Elderly women, but not men, experienced significant elevations in interdose morning plasma cortisol levels over 3 weeks of chronic treatment with alprazolam (0.5 mg b.i.d.) compared to placebo. In addition, higher morning plasma cortisol levels were significantly associated with better cognitive performance but not with higher plasma drug levels or greater degree of tolerance development to an acute alprazolam challenge.


CONCLUSIONS
Elderly females experienced a greater interdose activation of the HPA axis during treatment with therapeutic doses of alprazolam than men, which could be related to drug withdrawal.
Geriatric Psychiatry Program, Nathan S. Kline Institute, Orangeburg, NY, 10962, USA. pomara@nki.rfmh.org
Nunzio
N
Pomara
Lisa M
LM
Willoughby
James C
JC
Ritchie
John J
JJ
Sidtis
David J
DJ
Greenblatt
Charles B
CB
Nemeroff
D000368:Aged; D000525:Alprazolam / Q000097:blood / Q000494:pharmacology*; D003071:Cognition / Q000187:drug effects*; D004311:Double-Blind Method; D005260:Female; D005425:Flicker Fusion; D006801:Humans; D006854:Hydrocortisone / Q000097:blood*; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects; D008297:Male; D011939:Mental Recall / Q000187:drug effects; D008875:Middle Aged; D010913:Pituitary-Adrenal System / Q000187:drug effects; D012727:Sex Characteristics
D006854:Hydrocortisone; D000525:Alprazolam