Adjunctive Antipsychotics May Be Useful for Comorbid Chronic Pain and Depression
Having recently treated two patients with comorbid depressive disorder and intractable chronic pain (one with no underlying medical cause for the pain and one with pain out of proportion to organic findings), I decided to review the literature for common strategies for the psychopharmacologic treatment of pain in somatic symptom disorder.
Not surprisingly, most of the evidence has traditionally focused on antidepressants, particularly tricyclics, partly because of our knowledge about the role of serotonin and norepinephrine in the neurobiology of pain. Antidepressants are generally safe and well tolerated, and, obviously, quite useful for treating the comorbid mood and anxiety disorders that occur in patients with pain disorders. But what does one do when the depression, but not the chronic pain, resolves?
When faced with this clinical conundrum in the two patients mentioned above, I considered the role of adjunctive treatment with a neuroleptic. Recent research has begun to explore the role of the brain’s dopamine system in pain control (1) Dopamine-related illnesses, such as Parkinson’s disease, often involve pain-related symptoms (2), and patients with schizophrenia have been found to exhibit reduced pain sensitivity (3). This has led to the hypothesis that the degree of dopamine-system activation is inversely proportional to the degree of pain (4). A recent Cochrane Review meta-analysis of placebo-controlled studies in pharmacological interventions for somatoform disorders found evidence slightly in favor of combined treatment with SSRIs and an antipsychotic for medically unexplained symptoms (5).
In the two cases described above, I opted for treatment with aripiprazole because of its relatively more benign metabolic side-effect profile and the fact that both of my patients were particularly concerned about oversedation.
Though one patient experienced some degree of akathisia, which was not prohibitive, the drug was well tolerated overall. Both patients showed clinically significant improvement in pain over the course of two weeks and improved mobility and overall psychosocial function.
More rigorous evidence is certainly needed to address the role of neuroleptics in pharmacologic management of chronic pain. These drugs, as we know, can lead to significant metabolic side effects, and the side-effect risk must be weighed against the potential benefit for pain control on a case-by-case basis. However, the evidence thus far is promising and warrants further consideration of these drugs in the treatment of patients with mood disorders and somatic pain. ■
1. Leknes S, Tracey I. A common neurobiology for pain and pleasure. Nat Rev Neurosci . 2008; 9(4): 314-320.
2. Tinazzi M, Del Vesco C, Fincati E, et al. Pain and motor complications in Parkinson’s Disease. J Neurol Neurosurg Psychiatry. 2006; 77(7): 822-825.
3. Potvin S, Grignon S, Marchand S. Human evidence of a supra-spinal modulating role of dopamine on pain perception. Synapse. 2009; 63(5): 390-402.
4. Satoshi K, Yasuto K, Hirobumi M, Koji O, Shin-ichi K, Shin-ichi N. Four cases of chronic pain that improved dramatically following low-dose aripiprazole administration. Prim Care Companion CNS Disord. 2011; 13(2). pii: PCC.10l01078.
5. Kleinstäuber M, Witthöft M, Steffanowski A, van Marwijk H, Hiller W, Lambert MJ. Pharmacological interventions for somatoform disorders in adults. Cochrane Databse Ssyt Rev. 2014 Nov 7; 11: CD010628.
