Evidence-Based Reviews

Antipsychotics, dopamine, and pain

Current Psychiatry. 2020 January;19(1):25-29,31

References

1. Arbuck D, Pergolizzi J. Algopathy—acknowledging the pathological process of pain chronification. Pract Pain Manag. 2017;17(4):4,26-32.
2. Shin SW, Lee JS, Abdi S, et al. Antipsychotics for patients with pain. Korean J Pain. 2019;32(1):3-11.
3. D’Andrea G, Leone M, Bussone G, et al. Abnormal tyrosine metabolism in chronic cluster headache. Cephalalgia. 2017;37(2):148-153.
4. D’Andrea G, Granella F, Perini F, et al. Platelet levels of dopamine are increased in migraine and cluster headache. Headache. 2006;46(4):585-591.
5. Wolf EJ, Mitchell KS, Logue MW, et al. The dopamine D3 receptor gene, and posttraumatic stress disorder. J Trauma Stress. 2014;27(4):379-387.
6. den Ouden HEM, Daw ND, Fernandez G, et al. Dissociable effects of dopamine and serotonin on reversal learning. Neuron. 2013;80(4):1090-1100.
7. Nour MM, Dahoun T, Schwartenbeck P, et al. Dopaminergic basis for signaling belief updates, but not surprise, and the link to paranoia. Proc Natl Acad Sci U S A. 2018;115(43):E10167-E10176.
8. Zhu H, Clemens S, Sawchuk M, et al. Expression and distribution of all dopamine receptor subtypes (D(1)-D(5)) in the mouse lumbar spinal cord: a real-time polymerase chain reaction and non-autoradiographic in situ hybridization study. Neuroscience. 2007;149:885-897.
9. Wood PB, Schweinhardt P, Jaeger E, et al. Fibromyalgia patients show an abnormal dopamine response to pain. Eur J Neurosci. 2007;25:3576-3582.
10. Hagelberg N, Fossell H, Aalto S, et al. Altered dopamine D2 receptor binding in atypical facial pain. Pain. 2003;106(1-2):43-48.
11. Hagelberg N, Fossell H, Rinne JD, et al. Striatal dopamine D1 and D2 receptors in burning mouth syndrome. Pain. 2003;101(1-2):149-154.
12. Elman I, Borsook D. Common brain mechanisms of chronic pain and addiction. Neuron. 2016;89(1):11-36.
13. Siahposht-Khachaki A, Pourreza P, Ezzatpanah S, et al. Nucleus accumbens dopamine receptors mediate hypothalamus-induced antinociception in the rat formalin test. Eur J Pain. 2017;21(7):1285-1294.
14. Thompson T, Gallop K, Correll CU, et al. Pain perception in Parkinson’s disease: a systematic review and meta-analysis of experimental studies. Aging Res Rev. 2017;35:74-86.
15. Check JH. Chronic unremitting lower abdominal pain quickly abrogated following treatment with amphetamine. Clin Exp Obstet Gynecol. 2016;43(1):109-111.
16. Wilkes S. Bupropion. Drugs Today (Barc). 2006;42(10):671-681.
17. Frei K, Truong DD, Fahn S, et al. The nosology of tardive syndromes. J Neurol Sci. 2018;389:10-16.
18. Honkaniemi J, Liimatainen S, Rainesalo S, et al. Haloperidol in the acute treatment of migraine: a randomized, double-blind, placebo-controlled study. Headache. 2006;46(5):781-787.
19. Murray-Brown F, Dorman S. Haloperidol for the treatment of nausea and vomiting in palliative care patients. Cochrane Database Syst Rev. 2015;(11):CD006271.
20. Gaffigan ME, Bruner DI, Wason C, et al. A randomized controlled trial of intravenous haloperidol vs. intravenous metoclopramide for acute migraine therapy in the emergency department. J Emerg Med. 2015;49(3):326-334.
21. Weinman D, Nicastro O, Akala O, et al. Parenteral treatment of episodic tension-type headache: a systematic review. Headache. 2014;54(2):260-268.
22. Arnold LM, Auchenbach MB, McElroy SL. Psychogenic excoriation. Clinical features, proposed diagnostic criteria, epidemiology, and approaches to treatment. CNS Drugs. 2001;15(5):351-359.
23. Khouzam HR. Psychopharmacology of chronic pain: a focus on antidepressants and atypical antipsychotics. Postgrad Med. 2016;128(3):323-330.
24. Landsness EC, Wang LH, Bucelli RC. Ziprasidone as a potential abortive therapy for status migrainosus. Neurohospitalist. 2016;6(4):151-156.
25. Jimenez XF, Sundararajan T, Covington EC. A systematic review of atypical antipsychotics in chronic pain management: olanzapine demonstrates potential in central sensitization, fibromyalgia, and headache/migraine. Clin J Pain. 2018;34(6):585-591.
26. Fei L, Abrardi L, Mediati RD. Unexpected effect of aripiprazole on nociceptive pain. Ther Adv Psychopharmacol. 2012;2(5):211-212.
27. Markovic M, Gallipani A, Patel KH, et al. Brexpiprazole. Ann Pharmacother. 2017;51(4):315-322.
28. Gerrits M, de Greef R, Peeters P. Effect of absorption site on the pharmacokinetics of sublingual asenapine in healthy male subjects. Biopharm Drug Dispos. 2010;31(5-6):351-357.
29. Heo MH, Kim JY, Hwang I, et al. Analgesic effect of quetiapine in a mouse model of cancer-induced bone pain. Korean J Intern Med. 2017;32(6):1069-1074.
30. Tamburello AC, Lieberman JA, Baum RM, et al. Successful removal of quetiapine from a correctional formulary. J Am Acad Psychiatry Law. 2012;40(4):502-508.
31. Fountoulakis KN, Iacovides A, Kaprinis SG, et al. Diffuse muscle pain with quetiapine. Br J Psychiatry. 2003;182:81.
32. Shintani F. Diminished pain perception in schizophrenia. Lancet. 2010;376(9735):87.
33. Duric V, Banasr M, Franklin T, et al. Cariprazine exhibits anxiolytic and dopamine D3 receptor-dependent antidepressant effects in the chronic stress model. Int J Neuropsychopharmacol. 2017;20(10):788-796

Asenapine is an underutilized antipsychotic. Its mechanism of action spans multiple receptors and is less specific in individual receptor activity than other dopamine blockers. It is administered under the tongue due to poor absorption when swallowed, and its molecule has an anesthetic property that causes mouth and tongue numbness/paresthesia. This function may help patients with orofacial pain. Significant somnolence and weight gain (although less than with olanzapine) limit its use. Some patients cannot tolerate the taste.²⁸

Quetiapine is prescribed rather frequently due to its significant antianxiety effect. It is also reported to be beneficial in pain control.²⁹ Weight gain may be severe. In doses smaller than typically administered to patients with bipolar disorder or schizophrenia, quetiapine is widely prescribed off-label for sleep. In lower doses, it acts primarily as an antihistamine (hence the sedation), but at an increased dose it activates the adrenergic system, which offsets sedation. Quetiapine antagonizes H1 histamine and 5HT2C receptors, which may explain its associated sedation and weight gain. Constipation is common. Due to its relatively low risk for EPS, quetiapine is safer to prescribe in patients with Parkinson’s disease. It can cause withdrawal if abruptly discontinued, so it needs to be tapered. Quetiapine has become a commodity in the prison population because of its ability to diminish anxiety symptoms.³⁰ There are also reports that quetiapine may be associated with pain induction. This is consistent with the above-mentioned phenomenon that pain is associated with both the lack and excess of dopaminergic function.³¹ Pain perception is reported to be diminished in patients with schizophrenia,³² and quetiapine may increase pain just by improving cognition.

Cariprazine is typically well tolerated because of its benign metabolic profile. It does not increase the QT interval and is not sedating. Cariprazine is a D2 and D3 partial receptor agonist. This allows the medication to inhibit overstimulated dopamine receptors (a desirable effect in pain management) and induces them when the endogenous dopamine level is low (helping with cognition, volition, and attention). Pro-cognitive effects are always beneficial for patients with pain. Cariprazine produces less EPS due to more ventral striatum vs dorsal striatum activity. Mood improvement caused by this medication is attributed to its 5HT2A, 5HT2B, and 5HT2C inverse agonism, which modulates the serotonergic system. Cariprazine will likely have a positive future in pain management because it has shown efficacy in the chronic stress model.³³

A complex condition

No single medication or group of medications may be exclusively relied on for treating patients with chronic pain. Identifying alternatives to opioids for treating pain brings more attention to centrally-acting medications that may aid in the stabilization of the nervous system, which can decrease pathological pain perception and help patients cope with chronic painful conditions.

Bottom Line

Antipsychotics may be a valuable asset in the treatment of chronic pain, offering a potential alternative to prescribing opioids for pain. More research is needed to identify specific ways of using dopamine blockade or dopamine enhancement to help patients with chronic pain.

Continue to: Related Resource

Antipsychotics, dopamine, and pain

References

A complex condition

Bottom Line

Pages

Recommended Reading