Quetiapine and sleep
Despite widespread use of low-dose quetiapine for insomnia, the efficacy and safety for this indication is poorly documented by clinical trials (4–6). Only one randomised trial of its efficacy for primary insomnia has been conducted, on 13 patients (7). The results were inconclusive. An open, non-controlled study over six weeks with 18 patients with primary insomnia showed an improvement for some of the subjective sleep parameters (Pittsburgh Sleep Quality Index), but the time to sleep onset was not reduced (8).
In several studies of quetiapine use in psychosis, bipolar disorder or depression, the effects on sleep were also investigated (9, 10). It is difficult to distinguish between the positive effects of treatment of the primary disorder and on concomitant sleeping problems, but it was seen in these studies that quetiapine can also have a negative effect on sleep in patients with schizophrenia (10).
Three review articles from the years 2014–2018 all conclude that it is not advisable to use quetiapine for insomnia, mainly because of lack of documentation (4–6). The first of these concludes that the risk-benefit profile for use against insomnia is disadvantageous even for patients with another indication for using quetiapine (4).
It is assumed that central histamine H1 receptor blockade, and to a lesser extent alpha-1-antiadrenergic and antimuscarinergic properties, play an important part in the sedative effect of quetiapine (11, 12). It is estimated that almost 100 % of the H1 receptors and over 50 % of serotonin 5HT2a and dopamine D2 receptors are blocked by use of 50 mg quetiapine (12). In other words, there is evidence that quetiapine exerts an effect on several receptor systems even in low doses.
In studies of quetiapine in patients with schizophrenia, where higher doses are used, it is found that drowsiness as a side effect does not increase much with the dose, but most users find that they develop tolerance, so that sedation is less pronounced when quetiapine is used for several weeks (10). It seems reasonable that this also applies when quetiapine is used for insomnia. The development of tolerance is also a known effect of sedating antihistamines, which also have been used as sleeping aids. This use of inadequately documented drugs with an effect on many receptor systems for insomnia is not new in Norway, and has also previously been discussed in the Journal of the Norwegian Medical Association (14).