Letters to the Editor
Doxepin Increases Serum Cholesterol Levels
Dear Editor:
Doxepin is a well-known nonselective tricyclic antidepressant (TCA) that has been marketed in Germany for over 30 years and is still frequently applied. It causes common and group-specific side effects, including metabolic changes such as increases and decreases in blood sugar levels (1). Other metabolic changes in patients treated with TCAs have occasionally been reported. For example, increased serum cholesterol in 24 patients treated with imipramine for panic disorder was observed (2). Conversely, the same investigators also reported decreased high-density lipoprotein (HDL) cholesterol in patients on imipramine for panic disorder. Both depression patients and patients suffering from panic disorder showed an increase in the ratio of serum total cholesterol to HDL cholesterol under imipramine medication (3). After an average of 7 months of nortriptyline treatment, 26 depression patients showed significantly elevated levels of triglycerides and very-low-density lipoproteins (VLDL); however, they did not show significant changes in cholesterol levels (4). Further, it has been shown that the noradrenergic and specific serotonergic antidepressant (NaSSA) mirtazapine increases serum cholesterol to over 20% above the upper limit of normal in approximately 15% of patients (1).
We describe a patient who showed a significant isolated elevation of serum cholesterol while on monotherapy with doxepin.
Case Report
A 32-year-old white woman suffering from severe recurrent depression without psychotic symptoms, diagnosed according to ICD-10 criteria, had been on venlafaxine for 20 weeks, with serum cholesterol levels within the normal range (is 201 to 221 mg/dL). She switched from venlafaxine to doxepin, and by week 21, her cholesterol rose to 271 mg/dL. In week 25, her cholesterol reached a maximum level around 320 mg/dL, which persisted for 20 more days. After she stopped taking doxepin and switched to reboxetine in week 27, her serum cholesterol gradually fell within 3 weeks from 312 mg/dL to 209 mg/dL. During this time, reboxetine was given as an antidepressant. Throughout the entire period, triglyceride levels were within the normal range.
Discussion
At present, there are limited and contradictory data with respect to changes in cholesterol levels in patients on anti- depressant medications. Apart from limited data on TCAs, there are also reports on the effects of other antidepressants on lipid metabolism. A prospective study described a cholesterol-lowering effect of fluvoxamine (5). In a controlled study comparing fluoxetine and trazodone, the trazodone group, but not the fluoxetine group, exhibited significantly decreased cholesterol after 6 weeks of treatment (6). Elevated cholesterol levels during treatment with antidepressant medications appears to be noteworthy from 2 perspectives.
First, it is presumed that degeneration of minor cerebral vessels, possibly owing to impaired lipid metabolism, leads to a disruption of the frontosubcortical circuits that regulate mood, cognition, and movement (7). If TCAs elevate cholesterol levels, they may increase the risk of vascular depression, which would also be an unwanted side effect of this medication.
Second, since the early 1990s, a correlation between serum cholesterol levels and suicidal ideation or depression has been the subject of debate. To date, the reported results are contradictory; they range from increased suicide risk in persons with low serum cholesterol levels (8,9) to improved mood with dietary lowering of serum cholesterol (10) and include a nonnegative effect on mood symptoms (11). It is possible that low serum levels or lowering of the serum cholesterol correlate differently to mood symptoms in emotionally healthy persons and in depression patients, that a decrease in cholesterol owing to diet or owing to treatment with cholesterol-lowering medications produces different effects, and that this affects the sexes differently. To our knowledge, this is the first report observing increased serum cholesterol levels in a patient treated with doxepin.
Besides the need to examine the correlation of mood symptoms and the serum levels of various lipid fractions, additional studies, including prospective studies, of the changes in serum cholesterol and triglyceride levels during therapy with TCAs and other antidepressants are necessary. We recommend screening patients treated with TCAs for changes of serum cholesterol levels, especially patients at risk for cardiovascular diseases.
References
1. Bezchlibnyk-Butler KZ, Jeffries JJ. Clinical handbook of psychotropic drugs. Seattle, Toronto, Goettingen, Bern: Hogrefe and Huber Publishers; 2002.
2. Yeragani VK, Balon R, Pohl R, Ramesh C. Imipramine treatment and increased serum cholesterol levels. Can J Psychiatry 1989;34:845.
3. Yeragani VK, Pohl R, Balon R, Ramesh C, Glitz D. Increased serum total cholesterol to HDL-cholesterol ratio after imipramine. Psychiatr Res 1990;32:207–9.
4. Pollock BG, Perel JM, Paradis CF, Fasiczka AL, Reynolds CF 3rd. Metabolic and physiologic consequences of nortriptyline treatment in the elderly. Psychopharmacol Bull 1994;30:145–50.
5. de Zwaan M, Nutzinger DO. Effect of fluvoxamine on total serum cholesterol levels during weight reduction. J Clin Psychiatry 1996;57:346–8.
6. Perry PJ, Garvey MJ, Dunner DL, Rush AJ, Kyhl J. A report of trazodone-associated laboratory abnormalities. Ther Drug Monit 1990;12:517–9.
7. Hickie I, Simons L, Naismith S, Simons J, McCallum J, Pearson K. Vascular risk to late-life depression: evidence from a longitudinal community study. Aust N Z J Psychiatry 2003;37(1):62–5.
8. Papassotiropoulos A, Hawellek B, Frahnert C, Rao GS, Rao ML. The risk of acute suicidality in psychiatric inpatients increases with low plasma cholesterol. Pharmacopsychiatry 1999;32(1):1–4.
9. Ellison LF, Morrison HI. Low serum cholesterol concentration and risk of suicide. Epidemiology 2001;12:168–72.
10. Weidner G, Connor SL, Hollis JF, Connor WE. Improvements in hostility and depression in relation to dietary change and cholesterol lowering. The Family Heart Study. Ann Intern Med 1992;117:820–3.
11. Coutu MF, Dupuis G, D’Antono B. The impact of cholesterol lowering on patients’ mood. J Behav Med 2001;24:517–36.
Veit Roessner, MD
Joachim Demling, MD
Stefan Bleich, MD
Erlangen, Germany
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