Seroquel (Quetiapine) - does it work for insomnia?
In recent years, doctors have begun to prescribe Seroquel for sleep even though it is primarily used as an antipsychotic with sedation as a secondary effect. What is the clinical evidence behind Seroquel for insomnia, and is it effective?
What is Seroquel (Quetiapine)?
Prescription sleeping pills, such as Ambien or Xanax, can lead to addiction, especially if the dosage is not well-controlled. As such in recent years, doctors have begun to prescribe Seroquel for sleep even though it is primarily used as an antipsychotic with sedation as a secondary effect. 
Physician guidelines recommend that seroquel should primarily be prescribed for the treatment of schizophrenia, depression, acute mania, or as an adjunctive drug in major depressive disorder. However, it is increasingly being prescribed off-label in the treatment of insomnia, anxiety, and post-traumatic stress disorder. Although seroquel has a good safety profile and is non-addictive, the evidence justifying the use of Seroquel for insomnia is scarce. At the same time, there are many potentially harmful side effects. 
Is Seroquel useful for treating Insomnia?
Seroquel can improve symptoms that may interfere with sleep, such as alleviating feelings of anxiety and depression. Therefore, it can be tricky to assess its effectiveness as a sleeping aid when the drug is designed to improve symptoms that can contribute to poor sleep. To determine whether Seroquel has a direct effect on sleep, we can look at studies with healthy volunteers who show no signs of psychiatric illness. 
One study evaluated 14 healthy men who were given a placebo or Seroquel at doses of 25 mg and 100 mg for three consecutive nights. Both doses of Seroquel produced statistically significant improvements in objective and subjective sleep scores, including:
- total sleep time
- sleep efficiency
- sleep latency
- duration of stage N2 sleep.
Despite these positive effects, a dose of 100 mg was found to reduce the amount of REM sleep, a stage of sleep important for our emotional well-being.
The 100 mg dose also increased the number of periodic leg movements and two subjects taking quetiapine experienced orthostatic hypotension, which is a drop in blood pressure when a person goes from sitting to standing. 
How long does Seroquel make you sleepy?
Sedation is a side effect that contributed to the use of Seroquel for sleep. There are tablets with an immediate and produced release. With immediate-release tablets, maximum levels are reached after 1.5 hours. With produced-release tablets, it can take up to 6 hours after administration. The sedative effect occurs almost immediately, while other effects of the therapy are achieved only after two to three, even six weeks. 
In another study of people with primary insomnia, 25 participants received either 25 mg of Seroquel or a placebo. No significant improvements were seen in how long people slept, how quickly they fell asleep, their alertness during the day, or their sleep satisfaction.
A more recent study on healthy volunteers attempts to induce insomnia by using traffic noise to keep people awake. They found that Seroquel 50 mg increased sleep continuity and total sleep time compared to placebo. 
Can Seroquel disturb your sleep and in what ways?
Due to their action on histamine receptors, second-generation antipsychotics and Seroquel usually cause sedation. However, Seroquel can also interfere with sleep.
Seroquel has properties that increase sleep latency (decreasing the time to fall asleep), which can be attributed to its serotonergic effect.  Other side effects include dizziness, weakness, shortness of breath, headaches, fevers, dry mouth, weight gain, increased appetite, irregular heartbeat, stomach problems, swelling of the extremities, and suicidal thoughts.
In one clinical trial, two patients who were using low-dose quetiapine for insomnia stopped taking the drug. The reason was akathisia - a movement disorder characterized by a feeling of inner restlessness and the inability to remain still. 
In another study, following low-dose quetiapine treatment for insomnia in people with Parkinson’s disease, two of 13 participants stopped using the drug because of worsening restless legs symptoms. 
Does the current evidence justify the use of Seroquel for insomnia?
While there is some evidence that Seroquel can improve sleep in healthy subjects, there is insufficient evidence that it is effective for patients with primary insomnia. It is also inconclusive whether the benefits of treating insomnia with quetiapine outweighs the potential risks. [7, 8, 9]
Before prescribing quetiapine for the treatment of insomnia, a general practitioner or psychiatrist should carefully examine the reasons why it is a better choice compared to benzodiazepines that have stronger clinical evidence. A commonly cited reason for avoiding the use of traditional sleeping pills to treat insomnia is the concern that they have dependency risks. That is why physicians are looking to prescribe non-addictive alternatives. However, repeated studies have shown that quetiapine has the potential to be abused too. Side effects such as hangover symptoms the next morning and fatigue during the day are signals that patients should be cautious. Seroquel cannot cure sleep problems, it only masks them.
In summary, Seroquel should not be recommended for primary insomnia until there is more clinical evidence of its effectiveness. Recent clinical studies on Seroquel also raise serious questions about its suitability as a substitute for benzodiazepines. [7, 8] In general, cognitive behavioral therapy for insomnia (CBT-I), and not medication, should be the recommended first-line treatment for adults with primary insomnia.
Vania Modesto-Lowe, MD, MPH, Agata K. Harabasz, MD and Sophia A. Walker, MD. Quetiapine for primary insomnia: Consider the risks. Cleveland Clinic Journal of Medicine May 2021, 88 (5) 286-294; DOI: https://doi.org/10.3949/ccjm.88a.20031
Sankaranarayanan J, Puumala SE. Antipsychotic use at adult ambulatory care visits by patients with mental health disorders in the United States, 1996-2003: national estimates and associated factors. Clin Ther. 2007 Apr;29(4):723-41. doi: 10.1016/j.clinthera.2007.04.017. PMID: 17617297
Tassniyom K, Paholpak S, Tassniyom S, Kiewyoo J. Quetiapine for primary insomnia: a double blind, randomized controlled trial. J Med Assoc Thai 2010;93:729–34.
Catalano G, Grace JW, Catalano MC, Morales MJ, Cruse LM. Acute akathisia associated with quetiapine use. Psychosomatics. 2005 Jul-Aug;46(4):291-301. doi: 10.1176/appi.psy.46.4.291. PMID: 16000672.
Juri C, Chaná P, Tapia J, Kunstmann C, Parrao T. Quetiapine for insomnia in Parkinson disease: results from an open-label trial. Clin Neuropharmacol. 2005 Jul-Aug;28(4):185-7. doi: 10.1097/01.wnf.0000174932.82134.e2. PMID: 16062098.
Pierre JM, Shnayder I, Wirshing DA, Wirshing WC. Intranasal quetiapine abuse. Am J Psychiatry. 2004 Sep;161(9):1718. doi: 10.1176/appi.ajp.161.9.1718. PMID: 15337673.
Erdoğan S. Madde Kullanim Bozukluklarinda Ketiyapinin Yeri, Kötüye Kullanim ve Bağimlilik Olasiliği: Bir Gözden Geçirme [Quetiapine in substance use disorders, abuse and dependence possibility: a review]. Turk Psikiyatri Derg. 2010 Summer;21(2):167-75. Turkish. PMID: 20514567.
Wine JN, Sanda C, Caballero J. Effects of quetiapine on sleep in nonpsychiatric and psychiatric conditions. Ann Pharmacother. 2009 Apr;43(4):707-13. doi: 10.1345/aph.1L320. Epub 2009 Mar 18. PMID: 19299326.