What psychiatric medications are contraindicated or should be used with caution in patients with Myasthenia Gravis (MG)?

Psychiatric Medications in Myasthenia Gravis: Safety Profile

Contraindicated Psychiatric Medications

Barbiturates, particularly butalbital-containing medications like Fioricet, are contraindicated in myasthenia gravis due to their potential to worsen neuromuscular transmission and cause respiratory compromise. 1

Barbiturate-Specific Risks

• Barbiturate-containing medications pose particular risk for respiratory compromise in patients with active, symptomatic myasthenia gravis 1
• These agents directly impair neuromuscular transmission and can precipitate myasthenic crisis 1
• If barbiturates must be used despite contraindication, close monitoring is required for worsening muscle weakness, respiratory compromise, and changes in bulbar function (speech, swallowing) 1

Psychiatric Medications Requiring Extreme Caution

Atypical Antipsychotics

Long-acting risperidone should be used with extreme caution or avoided in myasthenia gravis patients, as it can cause persistent worsening of myasthenic symptoms that may not respond to plasma exchange. 2

• A documented case report showed worsening myasthenia 2 weeks after long-acting risperidone injection, with symptoms persisting despite plasma exchange due to the drug's prolonged pharmacokinetics 2
• The anticholinergic properties of antipsychotic drugs have the potential to worsen myasthenia 2
• If atypical antipsychotics are necessary, short-acting formulations allow for rapid discontinuation if symptoms worsen 2

Muscle Relaxants

Methocarbamol is contraindicated in myasthenia gravis as it interferes with the effects of pyridostigmine bromide, the primary treatment for MG. 3

• Orphenadrine is also contraindicated in myasthenia gravis due to its anticholinergic properties 3
• These medications can directly antagonize the therapeutic effects of acetylcholinesterase inhibitors used to treat MG 3

Benzodiazepines

Benzodiazepines can be used cautiously for anxiety and insomnia in myasthenia gravis, but require careful monitoring for respiratory depression, particularly in patients with bulbar or respiratory muscle involvement. 3, 4

• Infrequent, low doses of agents with short half-lives (lorazepam, oxazepam, temazepam) are least problematic 3
• Regular use can lead to tolerance, cognitive impairment, and paradoxical agitation in approximately 10% of patients 3
• The sedative effects may compound respiratory muscle weakness 4

Psychiatric Medications That Are Safer Options

Antidepressants

SSRIs may be used cautiously in myasthenia gravis patients and are not specifically contraindicated. 1

• SSRIs represent the safest class of antidepressants for MG patients when psychiatric treatment is needed 1
• Tricyclic antidepressants should be avoided due to their anticholinergic properties, which can worsen neuromuscular transmission 4
• Before prescribing any psychiatric medication, consultation with neurology is recommended to determine the safest alternatives 1

Mood Stabilizers

Trazodone can be used for agitation and insomnia in MG patients, starting at 25 mg daily with maximum doses of 200-400 mg daily in divided doses. 3

• Use with caution in patients with premature ventricular contractions 3
• Divalproex sodium is generally better tolerated than other mood stabilizers, with initial dosing of 125 mg twice daily titrated to therapeutic blood levels (40-90 mcg/mL) 3
• Monitor liver enzyme levels with divalproex sodium 3

Critical Pre-Treatment Assessment

Before prescribing any potentially problematic psychiatric medication, assess current symptom control, disease stability, and respiratory function (vital capacity and negative inspiratory force). 1

• Regular pulmonary function assessment is crucial in patients with generalized myasthenia gravis to monitor for respiratory compromise 1, 5
• Approximately 50% of patients with ocular myasthenia may develop generalized myasthenia within a few years, requiring ongoing vigilance 1, 5
• Patients with active, symptomatic, generalized MG are especially vulnerable to drug-induced exacerbations 6

Monitoring Protocol for Necessary Psychiatric Medications

If a potentially problematic psychiatric medication must be used, monitor for worsening muscle weakness, respiratory difficulties, changes in speech or swallowing (bulbar symptoms), and double vision (diplopia). 1

• Establish baseline respiratory function before initiating treatment 1
• Schedule follow-up within 1-2 weeks of starting any new psychiatric medication 2
• Educate patients to report any new or worsening weakness immediately 6
• Have a plan for rapid discontinuation if symptoms worsen 2

Common Pitfalls to Avoid

• Do not assume stable MG patients are immune to drug-induced exacerbations - while stable patients with few symptoms are less vulnerable, any MG patient can deteriorate with problematic medications 6
• Do not withhold necessary psychiatric treatment - MG patients require treatment for co-existing psychiatric conditions, but medication selection must be strategic 6, 4
• Do not use long-acting formulations when shorter-acting alternatives exist, as prolonged pharmacokinetics prevent rapid reversal if symptoms worsen 2
• Do not overlook drug interactions with acetylcholinesterase inhibitors (pyridostigmine), corticosteroids, and immunosuppressants used to treat MG 4