Volunteers, healthy antidepressant drugs

The antidepressant drug fluoxetine Prozac), another compound which promotes serotonergic neurotransmission in the brain, was also shown to reduce appetite and food intake in healthy volunteers (McGuirk and Sil-verstone 1990). It can be effective in the management of binge eating syndrome (see Chapter 6) and bulimia nervosa (see Chapter 5). Its use in uncomplicated obesity is more limited, as any beneficial effect wears off within a few months (Goldstein et al. 1994). 

The word "tolerability" is perhaps a little clumsy but it describes accurately what is assessed, namely how well the drug is tolerated by those to whom it is administered. This last qualification is necessary because there are many instances in which a drug is better tolerated or less well tolerated by young healthy volunteers than by patients. For example, anxiolytics and tricyclic antidepressants are usually far better tolerated by patients with depression than by healthy volunteers. However, healthy volunteer studies generally provide useful information about tolerability even if it may under- or overestimate tolerability in patients. Many adverse reactions wiU be directly related to the known pharmacological activity of the drug and are therefore predictable. 

Thymoleptics and thvmeretics are not happy pills , nor are they euphorics. In the case of endogenous depression there is a balancing out of pathological low mood, an effect that is normally obtained in two to three weeks or even longer in many cases. The first effect to become apparent in most cases of depression is the calming one, with the result that anxiousness, unrest and sleep disturbances can be reduced quickly and hence the patient s confidence in the treatment increases. Drugs that may be stimulating or cause euphoria in healthy volunteers, such as amphetamine, alcohol or cocaine, are not suitable for use as antidepressants. 

Fleishaker JC, Herman BD, Pearsotr LK, lorrita A, Mucci M. Evaluation of the potential pharmacokinetic/pharmaco-dynamic interaction between fluoxetine and reboxetine in healthy volunteers. Clin Drug Invest 1999 18 141-50. Herman BD, Fleishaker 1C, Brown MT. Ketoconazole inhibits the clearance of the enantiomers of the antidepressant reboxetine in humans. Clin Pharmacol Ther 1999 66(4) 374-9. 

Grislain L, Gele P, Bertrand M, Luijten W, Bromet N, Salvador C, Kamoun A (1990) The metabolic pathways of tianeptine, a new antidepressant, in healthy volunteers. Drug Metab Dispos 18 804-808... 

Considerable attention has been focussed on the antidepressant, tianeptine (23), which has included the development of a reverse-phase, ion-pair, liquid chromatographic method for the determination of the drug and its major metabolites in plasma, urine, and tissues <86JC115>. Further metabolic studies in healthy volunteers involving chromatographic and mass spectral analysis have also been reported <90mi 907-01 >. 

---