Venlafaxine fixes dulled sense of smell in major depression

Individuals with major depressive disorder exhibit diminished sensitivity to smell during an episode, but this event is resolved following treatment with venlafaxine, as shown in a study.

“Altogether, our results suggest an alteration of the early stages of olfactory information processing in the olfactory system of patients [having major depressive episodes (MDE)],” according to the investigators.

The alteration is characterized by deficits in threshold, discrimination, and identification (TDI) as well as perceived pleasantness of odours. “Threshold and pleasantness scores are restored after remission with venlafaxine treatment,” they said, adding that such a recovery is mediated by depression improvement.

In total, 69 treatment-naïve patients (mean age, 34.1 years; 66.7 percent female) with a current MDE in the context of major depressive disorder and 32 matched healthy individuals participated in the study. They underwent olfaction assessment, including a psychophysical test, the Sniffin’ Sticks test (threshold: T score; discrimination: D score; identification: I score; total score: TDI score), and pleasantness (pleasantness, neutral, and unpleasantness scores).

All patients received venlafaxine extended release at flexible doses depending on the treating psychiatrist. Mean doses were 184.1 and 196.4 mg/day after 1 and 3 months of treatment, respectively. More than three-fourths of patients (76.8 percent) also received benzodiazepines.

The MDE group had lower baseline TDI olfactory scores (mean, 30.0 vs 33.3; p<0.001), especially having problems with perceiving odour intensity as reflected by lower T scores (mean, 5.6 vs 7.4; p<0.01). Compared with controls, depressed patients also rated fewer odours as pleasant (mean, 7.5 vs 9.8; p<0.001) and more as neutral (mean, 3.5 vs 2.1; p<0.01). [Psych Med 2020;doi:10.1017/S0033291720003918]

Threshold, pleasantness, and neutral scores at baseline were independent of depression and anhedonia severity, the investigators noted.

Venlafaxine treatment led to a significant increase in T scores (p<0.01) and pleasantness scores (p<0.05), with the changes observed both at months 1 and 3. Furthermore, at month 3, both scores returned to normal among patients on remission but not among non-remitters. Neutral scores remained the same.

As pointed out earlier, the venlafaxine-induced changes in T and pleasantness scores were associated with improvements in Hamilton Depression Rating Scale-17 score, with mediating effect estimates of 0.43 (95 percent confidence interval [CI], 0.1–0.75) and 0.32 (95 percent CI, 0.01– 0.64), respectively.

“It is striking that only olfactory dimensions that rely more on early stages of olfactory information processing are decreased whereas those from higher cognitive levels (ie, discrimination and identification) remain unaltered,” they pointed out. “The biological mechanisms underlying these results should be further investigated.”

In conclusion, the investigators underscored a need to develop new therapeutic strategies focusing on olfaction for MDE patients and to test other antidepressants in those with smell disorders.