What is the best course of action for a 37-year-old female patient with persistent anxiety, paresthesias in her lower legs, feet, arms, and upper back, facial flushing, memory loss, and dizziness, who has been off her psychiatric medications (Prozac (fluoxetine), Lexapro (escitalopram), Depakote (valproate), Buspar (buspirone), Adderall (amphetamine and dextroamphetamine)) for 4 months, with mildly elevated inflammatory markers (elevated Erythrocyte Sedimentation Rate (ESR), elevated C-Reactive Protein (CRP)) and slightly elevated fasting glucose, after a negative initial workup?

Protracted Psychiatric Medication Withdrawal Syndrome

This patient is experiencing protracted withdrawal syndrome from abrupt discontinuation of polypharmacy, and the priority is to reinitiate at least one medication (preferably an SSRI like escitalopram or fluoxetine) at a low dose, then implement an extremely gradual taper over many months while addressing the mildly elevated glucose and inflammatory markers.

Understanding the Clinical Picture

This presentation is classic for medication withdrawal syndrome occurring after cessation of multiple psychotropic medications without proper tapering:

• Paresthesias, facial flushing, dizziness, and cognitive symptoms beginning 1 month after discontinuation are hallmark features of SSRI/SNRI discontinuation syndrome 1
• The "wanting to rip skin off" sensation represents severe akathisia-like withdrawal symptoms that can persist for months after abrupt cessation 1
• Memory fog and autonomic instability (dizziness, near-syncope) indicate ongoing CNS adaptation to the absence of multiple medications 2
• The negative workup effectively rules out alternative organic causes, making withdrawal syndrome the primary diagnosis 2

Why This Happened

The abrupt discontinuation of five medications simultaneously—two SSRIs (Prozac, Lexapro), one mood stabilizer (Depakote), one anxiolytic (Buspar), and one stimulant (Adderall)—created a perfect storm:

• SSRIs require gradual tapering over weeks to months to avoid withdrawal symptoms, with fluoxetine having the longest half-life but escitalopram requiring careful tapering 1
• Valproate (Depakote) discontinuation can cause rebound anxiety and neurological symptoms 1
• Buspirone cessation contributes to anxiety rebound 3
• Stimulant discontinuation causes fatigue, cognitive dysfunction, and mood changes 1

Immediate Management Strategy

Step 1: Medication Reinitiation

Restart a single SSRI at a low dose to stabilize the withdrawal syndrome:

• Escitalopram 5 mg daily or fluoxetine 10 mg daily are first-line choices given their efficacy for anxiety and favorable tolerability profiles 1, 3
• Maintain this dose for 4-6 weeks to allow symptom stabilization 1
• The goal is NOT to treat the original psychiatric conditions at this stage, but to mitigate withdrawal symptoms 2

Step 2: Address Metabolic Concerns

The fasting glucose of 116 mg/dL (prediabetic range) and mildly elevated inflammatory markers (ESR 29, CRP 15) require attention:

• Implement dietary modifications focusing on anti-inflammatory nutrition and glucose control 4
• These metabolic abnormalities may be contributing to neurological symptoms and should be addressed concurrently 4
• Recheck fasting glucose and HbA1c in 3 months to assess for progression toward diabetes

Step 3: Symptom Management During Stabilization

While waiting for medication reinitiation to take effect (2-4 weeks):

• Gabapentin 100-300 mg three times daily can help with paresthesias and anxiety symptoms during the withdrawal period 1
• Ensure adequate hydration and electrolyte balance as autonomic instability can worsen with dehydration
• Monitor orthostatic vital signs at each visit given the dizziness and near-syncope 1

The Proper Discontinuation Protocol (For Future Implementation)

Once symptoms stabilize (typically 2-3 months), if the patient still wishes to be medication-free, implement an extremely gradual taper:

Tapering Schedule

• Reduce the SSRI dose by 25% every 4-6 weeks (not 1-2 weeks as with some other medications) 5, 2
• For escitalopram: 5 mg → 2.5 mg → 1.25 mg → 0.625 mg before complete discontinuation 5
• Each dose reduction should be maintained for 4-6 weeks before the next reduction 1, 2
• The final doses may need to be compounded or achieved using liquid formulations 2

Monitoring During Taper

• Weekly phone contact during the first 2 weeks after each dose reduction 1
• In-person visits every 4 weeks to assess for withdrawal symptoms 1
• Use standardized rating scales (Hamilton Anxiety Scale) to track symptoms objectively 3
• Extend the taper interval to 8-12 weeks between reductions if withdrawal symptoms emerge 1, 5

Critical Pitfalls to Avoid

Do Not Restart Multiple Medications

• Avoid the temptation to restart all five medications that were discontinued 1
• Polypharmacy increases side effects and makes future discontinuation even more difficult 6
• A single SSRI addresses the withdrawal syndrome without recreating the original polypharmacy problem 2

Do Not Rush the Taper

• The most common error is tapering too quickly, which leads to protracted withdrawal symptoms lasting months to years 2, 7
• Patients who successfully discontinue psychiatric medications report that gradual tapering over 6-12 months was key to success 7
• 54% of patients attempting discontinuation experience severe withdrawal symptoms when tapering is too rapid 7

Do Not Dismiss Withdrawal as "Relapse"

• The timing (1 month after discontinuation) and symptom profile (paresthesias, flushing, autonomic instability) clearly indicate withdrawal, not relapse of the original psychiatric condition 2
• True relapse typically occurs later (3-6 months) and presents with return of original psychiatric symptoms, not new neurological symptoms 1

Supportive Interventions

While medication management is primary, adjunctive strategies improve outcomes:

• Psychoeducation about withdrawal syndrome reduces anxiety about symptoms 7
• Peer support from others who have successfully discontinued medications is rated as highly helpful by patients 7
• Lifestyle interventions including regular sleep schedule, exercise, and stress reduction support CNS recovery 4
• Cognitive-behavioral strategies for managing anxiety during the taper process 3

Long-Term Considerations

If Symptoms Persist Despite Proper Taper

• Consider maintaining a low-dose SSRI long-term (escitalopram 5-10 mg) rather than complete discontinuation 1
• Some patients require 12-24 months of maintenance therapy after stabilization 1
• The risk-benefit ratio favors continued low-dose treatment if withdrawal symptoms are severe and persistent 2

Monitoring for Relapse vs. Withdrawal

• Withdrawal symptoms: paresthesias, electric shock sensations, dizziness, flu-like symptoms 2
• Relapse symptoms: return of original anxiety, depression, or other psychiatric symptoms that prompted initial treatment 1
• This distinction guides whether to slow the taper (withdrawal) or increase the dose (relapse) 2