Dysosmia and drug tolerance with use of venlafaxine

Background

Dysosmia and dysgeusia are misperceptions of innocuous smell and taste stimuli, respectively, and can be debilitating to patients. While they have a variety of aetiologies, including being caused by psychiatric medications, they are rarely caused by selective serotonin reuptake inhibitors (SSRIs) or serotonin–norepinephrine reuptake inhibitors (SNRIs). There are very few case reports of this happening and none involving venlafaxine.1 2 In addition, there are no cases demonstrating the return of normal smell and taste with continued use of SSRIs or SNRIs.

Case presentation

A 57-year-old woman with a history of menopause, hypertension, hyperlipidaemia, type II diabetes with nephropathy and shoulder osteoarthritis presented to the primary care clinic for evaluation of a 1-year history of depressed mood, sleeping problems with insomnia, anhedonia, guilty feelings, decreased energy and difficulty concentrating. She denied a history of decreased or increased appetite or any suicidal or homicidal ideations. Blood pressure was 122/60, heart rate 88, temperature 36.7°C, weight 189 lbs, body mass index 29.6 and physical examination was remarkable only for depressed mood with mood-congruent affect. She was started on venlafaxine XR 75 mg orally daily.

At her 1-month follow-up appointment, she reported that she developed food avoidance because of a severe, bad smell that had arisen within several days of starting venlafaxine. She noted that her family told her the food smelled and tasted delicious and ‘that it was just her’. This included avoidance of eating foods that she previously enjoyed eating regularly that is, eggs, bacon, green beans, steak and chicken. The patient had no allergy symptoms and no history of allergic rhinitis. She had no concern for seizures. She also noted her depressed mood was improving although persistent. She reported no more crying episodes and a decreased desire to be isolated. She still had lost interest in activities she used to enjoy and still reported some difficulty with sleeping, but this was slowly improving as well. In addition, she had postmenopausal hot flashes and venlafaxine had controlled them. However, her food aversion led to a 7-pound weight loss that was directly a result of her food avoidance and not intentional weight loss. She reported no increased exercise to account for the weight loss and there were no other new symptoms or red flag symptoms. She was advised to stop venlafaxine and to switch to an alternative antidepressant, but she had just refilled the medication and was unable to afford a different medication and wanted to continue it given her improvement with her depression and hot flashes.

Forty-eight days later at follow-up, she reported complete resolution of her dysosmia and no further weight loss. She was eating normally and enjoying food again. Due to the persistence of some of her depressive symptoms, her dose was gradually titrated to venlafaxine XR 225 mg orally daily. With 8 years of follow-up, she did not have recurrence of dysosmia and her major depressive disorder and postmenopausal hot flashes remain controlled as it initially was on venlafaxine XR 225 mg orally daily.

Differential diagnosis

This patient was taking multiple other medications: amlodipine, rosuvastatin, insulin glargine, liraglutide and lisinopril. An alternative medication could have caused her dysosmia. However, she had no change in her medications or adjustment of doses when she started taking venlafaxine XR and when she developed the dysosmia. Furthermore, the dysosmia occurred within a few days of her starting venlafaxine XR and none of the other medications she is taking (or related medication classes) have been described to cause dysosmia. While medication interactions always need to be evaluated as a cause, on review of her medications, there are no known interactions that would cause dysosmia. Furthermore, medication interactions do not typically resolve without removing an offending medication (to resolve the interaction) and her dysosmia resolved spontaneously without further medication changes. Dysosmia can be caused by nasopharyngeal pathology. However, patient denied any symptoms or history of allergic rhinitis or rhinosinusitis, head trauma, recent upper respiratory infections or tobacco use. Intracranial neurological causes were unlikely since she had no other acute focal neurological deficits or complaints besides dysosmia, which ultimately resolved. This patient has diabetic nephropathy and nephropathy which has been weakly associated with smell loss, but not dysosmia. Furthermore, smell abnormalities would not be expected to start within several days of starting a new medication and also not expected to resolve with ongoing nephropathy. Lastly, her weight loss could have been intentional since she was overweight and she could have been trying to lose weight, but she denied trying to lose weight, did not increase exercise, and did not start a new dietary plan. Patient also directly cited her aversion to food and weight loss as being secondary to the dysosmia symptoms. Furthermore, she did not try any new foods and was having dysosmia to foods that she previously ate regularly (that had been enjoyable to her in the past). Olfactory hallucinations are also in the differential diagnosis, but olfactory hallucinations occur when there is a smell perception (typically malodorous) without a stimulus, whereas dysosmia occurs when there is an altered smell perception when confronted with a stimulus. This patient only had altered smell when confronted with a stimulus. Thus, she did not have olfactory hallucinations. This patient did not have chemosensory testing, but this testing is helpful in diagnosing hyposmia and anosmia (in quantifying the ability to smell) and not in demonstrating dysosmia (altered sensation of smell), which was present in this case.

Treatment

Continued use of venlafaxine led to drug tolerance and the side effect, dysosmia, resolved. Subsequent increase of the dose of venlafaxine XR from 75 mg orally daily to 225 mg orally daily led to clinical improvement of her depression and postmenopausal hot flashes, without recurrence of dysosmia.

Outcome and follow-up

With 8 years of follow-up, the patient still reports continued benefit of venlafaxine XR 225 mg orally daily and has controlled major depressive disorder and postmenopausal hot flashes, without recurrent dysosmia, food aversion, weight loss, or any new side effects. Patient is alive and doing well.