I learned from a friend’s recent hospitalization that acute mood stabilizer withdrawal is dangerous. While her experience was not associated with surgery, it’s a scenario that we could easily encounter in the perioperative period. Details of patient history have been modified to protect privacy.

The Case

Louise (not her real name) is a 60-year-old, healthy woman, with bipolar disorder, well controlled for over 20 years with a combination of Divalproex Sodium (Depakote), Lamotrigine (Lamictal), and Bupropion (Wellbutrin). While out of state, Louise developed vertigo and persistent nausea and vomiting from what was later diagnosed as a severe vertiginous migraine. She was admitted to the emergency room on day 3 of her illness.

Hospital Course

Louise told the admitting physicians her medications. The ER physicians, worried about stroke and/or possible complications from those medications, held them pending work-up. They did not contact her primary care MD to consult. Louise’s husband, out of the country at the time, contacted me to help if I could.

Blood work, an MRI, and a CT scan came back negative. On day 2 of hospitalization, Louise now 4 days without mood stabilizers, felt agitated and restless. Her fingers fumbled, preventing texting. Short term memory lapses frightened her. Louise couldn’t coordinate her arms and legs to roll out of bed. Ataxia prevented her from walking without help. Electric shocks jolted her feet whenever they touched the floor.

Her MDs, alarmed at the progression of neurologic symptoms, feared they had missed something serious. They continued to withhold her meds in order to avoid “confusing the picture”. They performed a CT scan with contrast. Negative.

By hospital day 3 her symptoms worsened. Her attending repeated the CT with contrast. Still negative. Emotionally distraught and angry, Louise feared she would hurt someone unintentionally. Progress notes documented that she was increasingly argumentative about demanding her medications, which they continued to withhold.

I tried calling her attending MD multiple times but was unsuccessful. Therefore, I finally left a message with the charge nurse suggesting that Louise’s symptoms were consistent with withdrawal from mood stabilizers. Louise finally received her meds on day 4 of hospitalization (almost 6 full days without meds). Her symptoms immediately lessened.

Discharge and Aftermath

On hospital day 5, the attending discharged her to her husband’s care. The hospital apologized, filled out an incident report, and told her they would alert their physicians to the risk of acute mood stabilizer withdrawal.

Louise needed a wheelchair at the airport to return home. Her fine motor control and hand tremor mostly resolved after 48 hours, although she had difficulty buttoning shirts for a few weeks. It took Louise 3 weeks before the ataxia resolved to the point that she could ambulate without a walker. During this time, she had several falls and broke 3 ribs. At 2 months she said she felt 95% normal.

Withdrawal from Mood Stabilizers

More than one billion people, or one in seven people, experience mental health or substance use disorders globally. [1] Doctors increasingly prescribe psychotropic drugs for non-psychiatric conditions, such as migraine, weight loss and chronic pain. We anesthetize patients taking mood stabilizers all the time.

Most research concentrates on anti-depressants. Historically, providers considered recurrence of the mental illness to be the main risk of acute withdrawal from mood stabilizers. They believed that other withdrawal symptoms were minor and short lived. Guidelines for discontinuation of treatment favored short tapers. However, recent research shows that significant withdrawal symptoms frequently accompany short tapers. [2]

What Causes Withdrawal

Mood stabilizers don’t just modify neurotransmitter activity, they can also lead to changes in brain architecture. For example, serotonin reuptake inhibitors (SSRIs) block absorption of serotonin, increasing its levels in the brain. PET scans show that the brain reacts by decreasing the number and activity of its own serotonin receptors. Take away the SSRI, and the decreased number and function of receptors creates an imbalance leading to withdrawal. [2,3] PET scan changes can last months to years.

Severity of the Problem?

One review article found more than half of those taking antidepressants experience problems upon stopping — with nearly half of those rating their symptoms as severe. [4] Journal of Affective Disorders Reports published a survey of 1100 patients suffering withdrawal symptoms from anti-depressants. [5,6] It found that withdrawal had significant effects.

• 20% lost their jobs
• 25% said personal relationships were affected
• 40% had symptoms lasting 2 years or longer

As a result, some providers now recommend tapering doses much more slowly, perhaps as little as 5-10% at a time, to allow receptors time to adapt.

Symptoms of Withdrawal from Mood Stabilizers

Not everyone develops withdrawal symptoms. Long term use and higher doses seem associated with higher risk. My friend Louise was acutely withdrawn from not one, but 3 mood stabilizers all at once — meds she had taken for over 20 years. This no doubt added to the severity of her withdrawal symptoms.

Doctors sometimes attribute withdrawal symptoms to return of the mental illness that was being treated. However, even patients prescribed that class of drug to treat migraines, chronic pain, or chronic fatigue experienced withdrawal symptoms.

Common mood stabilizer withdrawal complaints include the following:

• Balance: dizziness, lightheadedness
• Control of movements: tremors, restless legs, ataxia, uneven gait, difficulty coordinating speech and chewing movements, loss of fine and gross motor control, involuntary muscle movements
• Unwanted feelings: mood swings, agitation, anxiety, anger, mania, depression, irritability, confusion — even paranoia or suicidal ideation.
• Impaired thought processes: impaired memory, impaired concentration
• Strange sensations: pain, muscle aches, fatigue, photophobia, hypersensitivity to sound, numbness, electric shock sensations
• Gastrointestinal: nausea, vomiting, cramps, diarrhea, or loss of appetite.
• Vasoactive: tachycardia, excessive sweating, flushing, or heat intolerance.
• Sleep changes: insomnia, unusual dreams or nightmares.
• Status epilepticus: withdrawal from anti-seizure meds in those with lower seizure threshold

Learnings?

 “Dr. Whitten”, I hear you saying. “I’m sorry your friend had such a bad experience. But, obviously no one on my anesthesia team would ever acutely discontinue a patient’s mood stabilizers. Why should we be concerned?”

Knowledge is Power

Knowledge of pharmacology related to anesthesia includes drug actions, drug interactions, and also what happens when discontinuing a medication [1]. Before Louise’s experience, my biggest worry about perioperative mood stabilizers centered on preventing recurrence of mental illness. I never worried about development of serious neurologic dysfunction. Until Louise was hospitalized, I had never researched the effects of mood stabilizer withdrawal .

Don’t Forget The Big Picture

This is also a cautionary tale of losing sight of the bigger picture. Louise’s providers were so busy looking for the neurologic zebra, that they missed the diagnosis — that by withholding her medications they, themselves, had precipitated a neurologic crisis.

Sometimes Anesthesiologists Have to Play Internist

Having to diagnose something outside of our area of expertise is rare, but it happens. I once diagnosed secondary syphilis after spotting a rash on a young man’s palms. I sent a preop prostate patient to the ER for treatment of acute Steven’s Johnson Syndrome. And I recognized Complex Regional Pain Syndrome (Reflex Sympathetic Dystrophy) in a preop cataract patient, referring her postoperatively to the pain clinic. Sometimes keeping our patient safe means playing curbside internist.

Withdrawal From Mood Stabilizers Could Easily Happen Perioperatively

We care for patients who have been N.P.O. for days due to severe illness, gastrointestinal disasters, and sepsis. Occasional outpatients experience prolonged postoperative nausea and vomiting from narcotics. Noncompliant patients cross our paths all the time. Non-medical websites sometimes encourage patients to just stop taking their medications. We could easily encounter a patient withdrawing from mood stabilizers.

Involve Psychiatry and Pharmacy Early

Psychiatrists and pharmacists have much more experience dealing with psychoactive medications and their interactions than you do. Consult them if you have a patient at risk for mood stabilizer withdrawal . Had the attending MD caring for my friend Louise consulted with psychiatry, or a pharmacist, then her mood stabilizer withdrawal would likely have been recognized earlier and spared her both the ordeal, and the broken ribs.

We know that withholding beta blockers, anti-epileptics, and opioids, can precipitate significant perioperative complications. Therefore, we take great pains as anesthesia providers to avoid disruption in therapy. Mood stabilizers deserve the same attention. Our patient’s brain and mental health are in your hands. Please share this information with colleagues.

May The Force Be With You

Christine E. Whitten, author:
Anyone Can Intubate, A Step by Step Guide
And
Pediatric Airway Management, a Step by Step Guide

References

1. Harbell MW, Dumitrascu C, Bettini L, Yu S, Thiele CM, Koyyalamudi V. Anesthetic Considerations for Patients on Psychotropic Drug Therapies. Neurol Int. 2021 Nov 29;13(4):640-658. doi: 10.3390/neurolint13040062. PMID: 34940748; PMCID: PMC8708655.
   
2. Horowitz MA, Taylor D. (VOLUME 6, ISSUE 6, P538-546, JUNE 2019) Tapering of SSRI treatment to mitigate withdrawal symptoms. Lancet Psychiatry Published:March 05, 2019. DOI:https://doi.org/10.1016/S2215-0366(19)30032-X
   
3. Landau, MD, (2024 April). Many People wean off anti-depressants too quickly. That can be dangerous. National Geographic. Retrieved June 11, 2024 from https://www.nationalgeographic.com/premium/article/wean-off-antidepressants
   
4. Davies J, Read J. A systematic review into the incidence, severity and duration of antidepressant withdrawal effects: Are guidelines evidence-based?, Addictive Behaviors, Volume 97, 2019, Pages 111-121,ISSN 0306-4603, https://doi.org/10.1016/j.addbeh.2018.08.027.
   
5. Joanna Moncrieff, John Read, Mark Abie Horowitz. The nature and impact of antidepressant withdrawal symptoms and proposal of the Discriminatory Antidepressant Withdrawal Symptoms Scale (DAWSS), Journal of Affective Disorders Reports, Volume 16, 2024, 100765, ISSN 2666-9153,
   
6. Horowitz MA, Framer A, Hengartner MP, Sørensen A, Taylor D. Estimating Risk of Antidepressant Withdrawal from a Review of Published Data. CNS Drugs. 2023 Feb;37(2):143-157. doi: 10.1007/s40263-022-00960-y. Epub 2022 Dec 14. PMID: 36513909; PMCID: PMC9911477.