Central Nervous System Medications and Reproductive Endocrine Disorders

Introduction to Central Nervous System Medications

• Medications that affect the central nervous system, including some antiepileptic drugs, can potentially influence the hypothalamic-pituitary-gonadal axis, according to the American Academy of Neurology 1

Patient Populations at Risk

• Patients with epilepsy may already have a higher baseline risk of reproductive endocrine disorders, as noted by the American Academy of Neurology 1
• Elderly patients are more susceptible to CNS effects and may require lower starting doses of medications, and tricyclic antidepressants should be avoided due to anticholinergic effects, as recommended by the Centers for Disease Control and Prevention (CDC) 2

Medication Management

• The American Academy of Family Physicians recommends citalopram as a selective serotonin reuptake inhibitor (SSRI) for depression and anxiety disorders, metabolized primarily through the liver, with a starting dose of 10-20 mg once daily and a maximum dose of 40 mg daily 3
• Duloxetine can be considered as an alternative to gabapentin for neuropathic pain, which may also address depression, as recommended by the CDC 2
• Pregabalin requires monitoring of renal function regularly, as accumulation in patients with impaired renal function can lead to potentially fatal toxicity, as recommended by the BMJ 4
• The recommended dosing regimen for pregabalin is as follows:

• Dose adjustment is recommended in renal impairment for pregabalin, with a dose adjustment table as follows:

Contraindications and Precautions

• Pregabalin is contraindicated in pregnant women or women who may become pregnant without reliable contraceptive methods, as recommended by the American College of Obstetricians and Gynecologists 6
• Patients with a history of substance use disorders should be monitored closely due to the sedative effects of pregabalin, which may be reinforcing 7, 8
• Pregabalin can cause visual disturbances, especially at the start of treatment, with a potential for toxicity in patients with impaired renal function, as reported by the BMJ 4
• Patients taking pregabalin are at higher risk of cardiac adverse events and falls due to somnolence and dizziness, and consideration should be given to lower initial doses and slower titration 4
• Regular monitoring for peripheral edema in all patients on pregabalin is essential, with consideration of dose adjustment based on renal function, as recommended by the National Kidney Foundation 9
• Clinicians should monitor for emergence or worsening of depression, suicidal thoughts or behavior, and use pregabalin with caution when combined with other CNS depressants, as warned by the American Psychological Association 8

Alternative Therapies

• Duloxetine or gabapentin can be considered as alternatives to pregabalin for neuropathic pain management, with moderate evidence for efficacy, as suggested by the Annals of Internal Medicine and the American College of Physicians 10, 11
• Yoga, hypnosis, and acupuncture are recommended for chronic pain management, with moderate evidence, as per the Clinical Infectious Diseases guidelines 11
• Cognitive Behavioral Therapy (CBT) is recommended as a first-line treatment for chronic pain management, with strong, moderate evidence, as per the Clinical Infectious Diseases guidelines and other sources 11, 12
• Opioid analgesics should not be prescribed as first-line agents for long-term management of chronic neuropathic pain, with strong, moderate evidence, due to risks of addiction and other adverse effects, as recommended by the American Academy of Neurology 11
• Long-term NSAID use should be avoided due to potential cardiovascular, renal, and gastrointestinal risks, as warned by the Centers for Disease Control and Prevention 13

Treatment Guidelines

• For peripheral neuropathic pain, the first choice is pregabalin, followed by tricyclic antidepressants (TCAs) or serotonin-norepinephrine reuptake inhibitors (SNRIs) if contraindicated, and topical treatments or alpha-lipoic acid if there is an inadequate response, as per the American Diabetes Association recommendations 14
• For central neuropathic pain, the first choice is an SNRI (duloxetine), followed by a TCA if there is an inadequate response, and combination therapy for refractory cases, as per the American Diabetes Association recommendations 14
• For localized neuropathic pain, the first choice is topical capsaicin, followed by systemic therapy with pregabalin or an SNRI if there is an inadequate response, as per the Clinical Infectious Diseases guidelines 11
• Pregabalin should not be discontinued abruptly, as rapid discontinuation can lead to withdrawal syndrome, and a gradual reduction over at least one week is recommended 4