Residents’ Voices

Autism, pain, and the NMDA receptor

Natalie Lares, DO

s. G, a 36-year-old woman, pre- blood count, lipid panel, thyroid studies, sented to the emergency depart- urine drug screening, and urinalysis, were Mment (ED) requesting a neurologic unremarkable. Her blood pressure was evaluation. She told clinicians she had mildly elevated (141/82 mm Hg). “NMDA receptor encephalitis.” Ms. G’s eventual diagnosis was substance- Ms. G reported successful self-treatment induced mania (DXM). The DXM-containing of “life-long” body pain that was precipi- cough syrup and magnesium were discon- tated by multiple external stimuli (food, tinued in the hospital. She was stabilized on Dr. Lares is PGY-4 Psychiatry Resident, Department of Psychiatry, St. Mary social encounters, interpersonal conflict, lithium extended-release, 900 mg/d (blood Mercy Hospital, Livonia, Michigan.

etc.). Through her own research, she had level 0.8 mmol/L), and olanzapine, 10 mg/d Disclosure learned that both ketamine and magne- at bedtime. However, after discharge, Ms. G The author reports no financial sium could alter nociception in rats through resumed using Delsym, which resulted in 3 relationships with any companies whose products are mentioned in N-methyl-d-aspartic acid (NMDA) recep- subsequent psychiatric hospitalizations for this article, or with manufacturers of tor antagonism, and so she decided to try mania during the next year. competing products. treating her pain with Delsym, an over-the- I first treated Ms. G as an outpatient after counter cough syrup containing dextro- her second hospitalization. At that point, methorphan polistirex (DXM), which at high she was stable. Her mental status was doses acts as an NMDA receptor antagonist. calm and cooperative, and she had a lin- She said she was taking Delsym, 120 mg/d, ear thought process. At her baseline, in the and magnesium oxide, 600 mg/d. absence of mania, she had a blunted affect. In the ED, Ms. G had a labile affect, pres- She understood that DXM caused her to sured speech, and flight of ideas. She denied have manic symptoms, but she continued any history of psychiatric treatment, suicide to believe that Delsym and magnesium attempts, or substance abuse. Ms. G’s fam- cured her physical suffering and social inhi- ily reported she had been unusually social, bition. I noticed Ms. G would use figurative talkative, and impulsive. She was admitted language inappropriately. I later learned to the inpatient psychiatric unit with a diag- she had sensitivities to food textures and a nosis of mania. specialized interest in electronics. Because On psychiatric evaluation, Ms. G was of this, I suspected Ms. G was on the autism grandiose, irritable, and perseverative spectrum; she met several DSM-5 criteria about her aberrant symptoms. She felt she did not experience the world as other peo- ple did, but found relief from her chronic LET YOUR VOICE BE HEARD pain after taking Delsym. She was not tak- Current Psychiatry invites psychiatry residents ing other medications. Ms. G did not report to share their views on professional or clinical a family history of bipolar disorder or psy- topics for publication in Residents’ Voices. E-mail [email protected] for author chosis. Her laboratory results, including a guidelines. Current Psychiatry comprehensive metabolic panel, complete Vol. 18, No. 10 e3 Residents’ Voices

for autism spectrum disorder (ASD), par- researchers have found that suppression or ticularly deficits in social-emotional reci- excitation of the NMDA receptor can ame- procity, highly restricted interests, and liorate ASD symptoms, including social hyperreactivity to sensory input. withdrawal and repetitive behaviors.3 Upon routine lab screening, Ms. G Many individuals with ASD suffer from was found to have hypothyroidism, with sensory abnormalities, including a reduced a thyroid-stimulating hormone level of sensitivity to pain or a crippling sensitiv- 6.67 mcIU/mL. This resolved after discon- ity to various stimuli. Patients with ASD tinuing lithium. Olanzapine caused adverse may have difficulty describing these abnor- metabolic effects and also was discontin- malities, and as a result, they may be mis- ued. Ms. G remained euthymic without any diagnosed. One case report described a mood-stabilizing medication, except during 15-year-old girl diagnosed with social anxi- Clinical Point periods when she abused DXM, when she ety and chronic generalized pain when in 4 Ms. G’s case illustrates would again become manic. Eventually, her social situations. Pediatric rheumatologists motivation to avoid hospitalization would had diagnosed her with “amplified pain the importance promote her abstinence. syndrome.” When she presented to a men- of listening to our tal health clinic for a neurodevelopmental patients for more evaluation, she explained to clinicians how precise diagnostic Implications of NMDA receptor she simply “did not ‘get’ people; they are antagonism just empty shells” and subsequently was formulations The use of ketamine as an NMDA recep- given a diagnosis of ASD.4 tor antagonist for treating depression In psychiatric patients who have comor- and other psychiatric illnesses has gained bid substance use disorders, it is vital for momentum. Esketamine, the S-enantiomer clinicians to not only detect the presence of of racemic ketamine, is now available as an substance misuse, but also to understand FDA-approved intranasal formulation for what drives the patient toward abuse. treatment-resistant depression. Ketamine Ms. G’s case, with its combination of sub- stops afferent nociception to the brain and is stance abuse and ASD, illustrates the used as an analgesic (at low concentrations) importance of listening to our patients and anesthetic (at high concentrations).1 for more precise diagnostic formula- Dextromethorphan is abused as a recre- tions, which then shape our treatment ational drug because at high doses it works recommendations. similarly to both ketamine and phen- cyclidine. Individuals who abuse DXM References 1. Vadivelu N, Schermer E, Kodumudi V, et al. Role of ketamine can develop psychosis, motor/cognitive for analgesia in adults and children. J Anaesthesiol Clin impairment, agitation, fevers, hyperten- Pharmacol. 2016;32(3):298-306. 2. Martinak B, Bolis R, Black J, et al. Dextromethorphan in cough sion, tachycardia, and death.2 In patients syrup: the poor man’s psychosis. Psychopharmacol Bull. with ASD, researchers have identified 2017;47(4):59-63. 3. Lee E, Choi S, Kim E. NMDA receptor dysfunction in autism genetic variations of NMDA receptors that spectrum disorders. Curr Opin Pharmacol. 2015;20:8-13. are linked to dysfunction of these receptors.3 4. Clarke C. Autism spectrum disorder and amplified pain. Case Rep Psychiatry. 2015;2015:930874. doi: 10.1155/2015/ In animal models, as well as in humans, 930874. Discuss this article at www.facebook.com/ MDedgePsychiatry

Current Psychiatry e4 October 2019