What are the potential interactions between psychiatric medications and myasthenia gravis (MG)?

Psychiatric Drug Interactions with Myasthenia Gravis

Benzodiazepines are contraindicated in myasthenia gravis patients except when imminently dying, and several psychiatric medications can precipitate myasthenic crisis requiring immediate discontinuation. 1

Absolutely Contraindicated Psychiatric Medications

Benzodiazepines

• Benzodiazepines should be avoided in all myasthenia gravis patients except those who are imminently dying, due to severe risk of respiratory compromise 1
• This includes commonly used agents like lorazepam and midazolam, which carry warnings specifically for myasthenia gravis 1
• The respiratory depressant effects are particularly dangerous given the underlying neuromuscular weakness affecting respiratory muscles 2

Beta-Blockers

• Beta-blockers must be immediately discontinued if a patient develops myasthenia gravis symptoms, as they can worsen neuromuscular transmission and precipitate respiratory failure 1, 2
• This applies to beta-blockers used for anxiety or performance anxiety in psychiatric practice 1

High-Risk Psychiatric Medications Requiring Extreme Caution

Antipsychotics

First-Generation Antipsychotics:

• Haloperidol can be used but requires careful monitoring for extrapyramidal symptoms, orthostatic hypotension, and QTc prolongation 1
• Start at 0.5-1 mg orally or subcutaneously, with maximum 5 mg/24 hours 1
• May cause anticholinergic effects which could theoretically worsen myasthenic symptoms 1

Second-Generation Antipsychotics:

• Olanzapine: Start 2.5-5 mg orally or subcutaneously; reduce dose in older patients 1
  • Critical warning: Combining olanzapine with benzodiazepines has resulted in fatalities due to oversedation and respiratory depression 1
• Quetiapine: Start 25 mg orally; less likely to cause extrapyramidal symptoms but may cause orthostatic hypotension 1
• Risperidone: Start 0.5 mg orally; increased risk of extrapyramidal symptoms at doses >6 mg/24 hours 1

Third-Generation Antipsychotics:

• Aripiprazole: 5 mg orally or intramuscularly; less likely to cause extrapyramidal symptoms 1
• Monitor for cytochrome P450 2D6 and 3A4 drug interactions 1

Antidepressants

Selective Serotonin Reuptake Inhibitors (SSRIs):

• Sertraline (Zoloft) has been successfully used at 50 mg daily in myasthenia gravis patients with depression 3
• SSRIs are generally considered safer than other antidepressant classes in myasthenia gravis 3, 4

Tricyclic Antidepressants:

• Should be avoided due to anticholinergic effects that can worsen neuromuscular transmission 4

Anxiolytics (Non-Benzodiazepine)

• Hydroxyzine (Atarax): Has been used successfully at 50 mg three times daily for anxiety in myasthenia gravis patients 3
• Represents a safer alternative to benzodiazepines for anxiety management 3

Monitoring Requirements for Psychiatric Medications in Myasthenia Gravis

Baseline Assessment Before Starting Psychiatric Medications

• Measure negative inspiratory force (NIF) and vital capacity (VC) to establish respiratory baseline 5, 2
• Apply the "20/30/40 rule": vital capacity <20 ml/kg, maximum inspiratory pressure <30 cmH₂O, or maximum expiratory pressure <40 cmH₂O indicates high risk 5, 2
• Perform complete neurological examination focusing on ptosis, diplopia, dysphagia, and generalized weakness 1, 5

Ongoing Monitoring

• Frequent pulmonary function assessments with NIF and VC in patients with moderate to severe disease (MGFA class III-V) 5, 2
• Monitor for signs of respiratory fatigue: difficulty holding up head, slurred speech, trouble chewing or swallowing 5
• Watch for worsening muscle weakness, especially with repetitive activities 6
• Respiratory insufficiency may develop without obvious dyspnea symptoms 5

Management of Psychiatric Comorbidities in Myasthenia Gravis

Depression and Anxiety

• Depression and anxiety are common comorbidities in myasthenia gravis, affecting quality of life beyond motor symptoms 3, 4
• Mental health must be a clinical focus during treatment of somatic symptoms 3
• Psychiatric symptoms may overlap with myasthenic symptoms (fatigue, lack of energy, shortness of breath), leading to diagnostic confusion 4
• Psychopathological disturbances in exacerbated myasthenic patients are often temporary and reversible with adequate somatic therapy 7

Treatment Algorithm

1. Optimize myasthenia gravis treatment first before attributing all symptoms to psychiatric causes 4, 7
2. Choose SSRIs as first-line antidepressants (e.g., sertraline 50 mg daily) 3
3. Use hydroxyzine for anxiety instead of benzodiazepines (50 mg three times daily) 3
4. Avoid anticholinergic medications that can worsen neuromuscular transmission 4
5. Start all psychiatric medications at low doses and titrate slowly while monitoring respiratory function 1

Emergency Management of Drug-Induced Myasthenic Crisis

Immediate Actions

• Permanently discontinue the offending psychiatric medication 1, 2
• Admit to ICU for monitoring 1, 2
• Initiate high-dose corticosteroids: methylprednisolone 2-4 mg/kg/day IV or prednisone 1-1.5 mg/kg/day orally 1, 2
• Start IVIG 2 g/kg over 5 days (0.4 g/kg/day) OR plasmapheresis for 5 sessions 1, 2
• Perform daily neurological evaluations and frequent pulmonary function assessments 1, 2

Intubation Considerations

• Consider noninvasive positive-pressure ventilation first, even in patients with bulbar weakness 6
• If intubation necessary, avoid depolarizing paralytics (succinylcholine) entirely 6
• Use reduced doses (50-75% reduction) of non-depolarizing agents like atracurium or cisatracurium with train-of-four monitoring 8, 6
• Patients have increased sensitivity to non-depolarizing neuromuscular blockers due to reduced functional acetylcholine receptors 8

Common Pitfalls to Avoid

• Never assume psychiatric symptoms are purely functional in myasthenia gravis patients—they may represent worsening neuromuscular disease 4, 7
• Do not use benzodiazepines for anxiety even though they are first-line in other populations 1
• Avoid combining olanzapine with any benzodiazepine due to fatal respiratory depression risk 1
• Do not overlook medication-induced exacerbations when introducing new psychiatric drugs—symptomatic generalized myasthenia gravis patients are especially vulnerable 9
• Never use beta-blockers for performance anxiety or akathisia in myasthenia gravis patients 1, 2