Low-dose Trazodone Effective in Insomnia

Although the risk of benzodiazepine dependence may be overstated, alternatives in the pharmacological treatment of chronic insomnia are certainly welcome. One such candidate is trazodone (TRZ), a second-generation triazolopyridine antidepressant that possesses significant anxiolytic and sedative activity resulting from 5-HT2 and alpha-1 receptor blockade [5]. The drug has been shown to improve sleep efficiency, total sleep duration, deep sleep duration, and REM sleep duration and to reduce the duration of awakenings and stage 2 sleep in depressed insomniac patients [4]. It was also found to be useful in antidepressant-induced insomnia [3] and after detoxification in patients with alcoholism [2].

However, patients frequently complain of secondary effects, such as vegetative symptoms before sleep (tachycardia), very deep sleep (sometimes accompanied by incontinence), or prolonged hangover. As a result, several of them do not keep a positive image of this drug and wish to discontinue it.

A logical strategy was to use lower dosages than are commonly prescribed (50-100 mg).

Ten patients who had used trazodone at these dosages and appreciated its sleep-inducing and -maintaining properties but suffered from unwelcome secondary effects were invited to participate in an open trial. Using 5-mg capsules, they were asked to titrate their medication, in order to find the optimal balance between positive and negative effects. Two patients described their sleep as satisfying using as little as 5 mg of the substance; four, with 10 mg; three, with 15 mg; and one, with 20 mg).

According to these preliminary data, there is some reason to believe that trazodone is marketed at too high a dosage with regard to its sleep-acting properties, at least for a good fraction of the cases. Open-label and controlled studies should naturally confirm these findings. The potential overdosage, in turn, may provide a poor clinical impression of this otherwise quite valuable alternative to classical sleeping pills. This medication should be prescribed with a start-up strategy in mind, using very low dosages at first and remaining at that level in a certain number of cases.

Such a strategy is also in line with the new paradigms of individualized medicine, which suggests putting more stress on adjusting drug dosages as a function of a patient’s reaction, which is itself probably based a good deal on genetic variability [1].

References

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• 2 Le Bon O, Murphy J R, Staner L, Hoffmann G, Kormoss N, Kentos M, Dupont P h, Lion K, Pelc I, Verbanck P. A double-blind, placebo-controlled study of the efficacy of trazodone in alcohol post-withdrawal syndrome: polysomnographic and clinical evaluations.  J Clin Psychopharmacol. 2003;  23 (4) 377-383
• 3 Nierenberg A A, Adler L A, Peselow E. et al . Trazodone for antidepressant-associated insomnia.  Am J Psychiatry. 1994;  151 (7) 1069-1072
• 4 Saletu-Zyhlarz G M, Abu-Bakr M H, Anderer P. et al . Insomnia in depression: differences in objective and subjective sleep and awakening quality to normal controls and acute effects of trazodone.  Prog Neuropsychopharmacol Biol Psychiatry. 2002;  26 (2) 249-260
• 5 Silvestrini B, Valeri P. Trazodone, a new avenue in the treatment of depression.  Psychopathology. 1984;  17 (suppl 2) 3-14