The primary symptoms of menopause are genitourinary and vasomotor. The genitourinary syndrome of menopause (GSM) includes symptoms such as burning, irritation, dryness, dyspareunia, dysuria, and recurrent urinary tract infection. Vasomotor symptoms (VMS; hot flashes, night sweats) often disrupt sleep.

A nephrologist and longtime reader of The Medical Letter wrote us to say that our recent article entitled Drugs for Anxiety Disorders should have said more about the need for dosage adjustment of gabapentin (Neurontin, and others) and pregabalin (Lyrica, and others) in patients with renal impairment. Both drugs, he pointed out, are exclusively renally eliminated and can accumulate in patients with diminished renal function. Symptoms, which can include altered mental status, may develop so slowly that neither the patient nor the practitioner connect them to the drug. The resolution of adverse effects upon discontinuation can be slow.

Anxiety disorders (generalized anxiety disorder, panic disorder, social anxiety disorder, and various phobias) are the most common form of psychiatric illness. They can be treated effectively with cognitive behavioral therapy (CBT) and/or pharmacotherapy.

Cognitive behavioral therapy for insomnia (CBT-I) is recommended for initial treatment of chronic insomnia. CBT-I includes stimulus control, sleep education and hygiene, sleep restriction, relaxation training, and cognitive therapy. When CBT-I alone is not effective, pharmacologic treatment should be added.

Nonopioid drugs can be used in the treatment of many nociceptive and neuropathic pain conditions. For severe pain, especially severe chronic cancer pain, use of opioids may be necessary. Noninvasive nonpharmacologic treatments, including physical and psychological therapies, have been shown to improve pain and function in patients with some common chronic pain conditions and are unlikely to cause serious harms. A multimodal approach to analgesic therapy can increase pain control while reducing opioid use and adverse effects.

Difelikefalin (Korsuva – Vifor), an IV kappa opioid receptor (KOR) agonist, has been approved by the FDA for treatment of moderate to severe pruritus associated with chronic kidney disease (CKD) in adults on hemodialysis. It is the first drug to be approved for this indication and the first KOR agonist to become available in the US. Difelikefalin has not been studied in patients on peritoneal dialysis.

The primary symptoms of menopause are genitourinary (genitourinary syndrome of menopause; GSM) and vasomotor (VMS). Vulvovaginal atrophy can cause vaginal burning, irritation and dryness, dyspareunia, and dysuria, and increase the risk of urinary tract infections. Vasomotor symptoms ("hot flashes") cause daytime discomfort and night sweats that may disrupt sleep. Hormone therapy is the most effective treatment for both genitourinary and vasomotor symptoms.

The FDA has required new warnings in the labels of gabapentin (Neurontin, and others) and pregabalin (Lyrica, Lyrica CR, and generics) about the risk of life-threatening or fatal respiratory depression in patients with respiratory risk factors. Respiratory risk factors include chronic obstructive pulmonary disease (COPD) and concurrent use of opioids or other CNS depressants. Elderly patients are also at increased risk.

Irritable bowel syndrome (IBS) is a common disorder characterized by recurrent abdominal pain and altered bowel habits, often accompanied by bloating.IBS is classified according to the predominant bowel symptom as IBS with constipation (IBS-C), IBS with diarrhea (IBS-D), mixed type (IBS-M), or unclassified (IBS-U). Alterations in the microbiome, stress responses, sensory and motor function of the gut, and host genetic factors may be contributing factors. Since the exact cause of IBS is unknown, the goal of treatment is symptom control.

View the Table: Safety of Drugs for IBS in Pregnancy and Lactation

Anxiety disorders (generalized anxiety disorder, panic disorder, social anxiety disorder, and various phobias) are the most common form of psychiatric illness. They can be treated effectively with cognitive behavioral therapy (CBT) and/or pharmacotherapy. Obsessive-compulsive disorder and posttraumatic stress disorder are now considered separate entities in the Diagnostic and Statistical Manual of Mental Disorders (DSM-5); they can also be treated with CBT and many of the same drugs.

A lidocaine 1.8% patch (ZTlido – Scilex) has been approved by the FDA for treatment of pain associated with postherpetic neuralgia (PHN). A lidocaine 5% patch (Lidoderm, and generics) was approved earlier for the same indication and has been used off-label for treatment of other types of localized pain. Both of these patches are available only by prescription. Lidocaine 4% patches (Aspercreme, IcyHot, and others) are available over the counter for back, neck, shoulder, and joint pain.

Interim results of a double-blind, placebo-controlled trial suggest that off-label use of the anticholinergic drug oxybutynin may reduce the frequency and severity of hot flashes in women with breast cancer. Extended-release oral oxybutynin (Ditropan XL, and generics) has been shown to reduce the frequency and severity of hot flashes in healthy menopausal women.

Nonopioid drugs can be used in the treatment of many nociceptive and neuropathic pain conditions. Use of opioids for pain will be reviewed in a future issue.

View the Comparison Table: Some Oral Antiepileptic Drugs

Treatment of epilepsy should begin with a single antiepileptic drug (AED), increasing its dosage gradually until seizures are controlled or adverse effects become intolerable. If seizures persist, specialists generally recommend trying at least one and sometimes a second alternative drug as monotherapy before considering use of two drugs concurrently. When used for the appropriate seizure type, AEDs are roughly equivalent in efficacy. Drug choice is usually based on factors such as ease of use, adverse effects, drug interactions, presence of comorbidities, and cost.

Pharmacological treatment of insomnia includes prescription drugs, non-prescription medications, and "natural" remedies. Behavioral approaches such as cognitive behavioral therapy, which are not discussed here, are also used. Pharmacologic treatment and behavioral therapy are often combined.

Pain can be acute or chronic. The two major types of chronic pain are nociceptive pain and neuropathic pain. Nociceptive pain can be treated with nonopioid analgesics or opioids. Neuropathic pain is less responsive to opioids and is often treated with adjuvant drugs such as antidepressants and antiepileptics. Combining different types of analgesics may provide an additive analgesic effect without increasing adverse effects.

Treatment of epilepsy should begin with a single drug, increasing the dosage gradually until seizures are controlled or adverse effects become unacceptable. If seizures persist, expert clinicians generally prescribe at least one and sometimes a second alternative drug as monotherapy before considering use of two drugs at the same time. When used for the appropriate seizure type, antiepileptic drugs are roughly equivalent in efficacy. The choice of drug is usually based on factors such as ease of use, adverse effects, interactions with other drugs, presence of comorbid conditions and cost.

The FDA has approved ezogabine (ee-ZOE-ga-been; Potiga – GSK/Valeant) for oral adjunctive treatment of partial-onset seizures in adults. Ezogabine is available in Europe as retigabine (Trobalt).

The FDA has approved a topical 8% patch formulation of capsaicin (Qutenza – NeurogesX), available only by prescription, for local treatment of postherpetic neuralgia. Postherpetic neuralgia occurs after herpes zoster in about one third of patients ≥60 years old and can persist for months or even years.

Pain can be acute or chronic. Chronic pain has been broadly classified into two types: nociceptive and neuropathic. Nociceptive pain can be treated with nonopioid analgesics or opioids. Neuropathic pain is less responsive to opioids; adjuvant medicines such as antidepressants and anticonvulsants are often used to treat neuropathic pain. Combining different types of analgesics may provide an additive analgesic effect without increasing adverse effects.

The FDA has approved vigabatrin (vye gá ba trin; Sabril – Lundbeck) for oral use as add-on therapy for complex partial seizures in adults who are refractory to several antiepileptic drugs and as monotherapy for infantile spasms. Vigabatrin has been available in other countries for many years. Because of its potential for retinal toxicity, it will be available in the US only through a restricted distribution program called SHARE (Support, Help and Resources for Epilepsy). Prescribers and pharmacists distributing the drug must register, and patients must undergo visual field testing.

The FDA has approved lacosamide (Vimpat - UCB Pharma) for oral or intravenous (IV) use as add-on therapy in adults with partial-onset seizures.

Milnacipran (Savella - Forest), an oral selective serotonin and norepinephrine reuptake inhibitor (SNRI), is the third drug approved by the FDA for management of fibromyalgia. The 2 others are pregabalin, a gammaaminobutyric acid (GABA) analog also approved for treatment of diabetic neuropathy, post-herpetic neuralgia and epilepsy, and duloxetine, an SNRI also approved for treatment of depression, diabetic neuropathy and generalized anxiety disorder.

Many drugs can cause psychiatric symptoms, but a causal connection is often difficult to establish. Psychiatric symptoms that emerge during drug treatment could also be due to the underlying illness, previously unrecognized psychopathology, or psychosocial factors. The withdrawal of some drugs can cause symptoms such as anxiety, psychosis, delirium, agitation or depression.

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Duloxetine (Cymbalta - Lilly) is the second drug to be approved by the FDA for treatment of fibromyalgia. Pregabalin (Lyrica), which is also approved for treatment of neuropathic pain and epilepsy, was the first. Duloxetine is a selective serotonin and norepinephrine reuptake inhibitor (SNRI) that is already marketed for treatment of depression and diabetic neuropathy.

Treatment of epilepsy should begin with a single drug, increasing the dosage gradually until seizures are controlled or adverse effects become unacceptable. If seizures continue and further dosage increases appear inadvisable because of adverse effects, most Medical Letter consultants generally prescribe at least one and sometimes a second alternative drug as monotherapy before considering use of two drugs at the same time. Most antiepileptic drugs initially approved by the FDA only as adjunctive therapy for partial seizures may also be effective for other types of seizures and as monotherapy. Studies suggest that when used for the appropriate seizure type, antiepileptic drugs are roughly equivalent in efficacy. The choice of a drug is usually based on factors such as ease of use, adverse effects and cost.

Pregabalin (Lyrica - Pfizer) is the first drug approved by the FDA for management of fibromyalgia. When it was first marketed, pregabalin, which is structurally similar to gabapentin (Neurontin, and others), was approved for treatment of neuropathic pain associated with postherpetic neuralgia and diabetic peripheral neuropathy and for adjunctive treatment of partial onset seizures in adults with epilepsy. It has also been prescribed off-label for other types of neuropathic pain such as sciatica.

Treatment of epilepsy should begin with a single drug, increasing the dosage gradually until seizures are controlled or adverse effects become unacceptable. If seizures continue and further dosage increases appear inadvisable because of adverse effects, most Medical Letter consultants generally prescribe at least one and sometimes a second alternative drug as monotherapy before considering use of two drugs at the same time. Most antiepileptic drugs initially approved by the FDA only as adjunctive therapy for partial seizures may also be effective for other types of seizures and as monotherapy.

Pregabalin (Lyrica - Pfizer), a structural analog of gamma-aminobutyric acid (GABA) similar to gabapentin (Neurontin - Pfizer, and others), which recently became available generically, has been approved by the FDA for treatment of neuropathic pain associated with postherpetic neuralgia (PHN) and diabetic peripheral neuropathy (DPN), and for adjunctive treatment of partial onset seizures in adults with epilepsy.

Duloxetine hydrochloride (Cymbalta - Lilly), a selective serotonin and norepinephrine reuptake inhibitor (SNRI) available for treatment of depression, has also been approved by the FDA for treatment of neuropathic pain associated with diabetic peripheral neuropathy (DPN). Duloxetine is one of two drugs approved specifically for management of neuropathic pain due to diabetes; the other, pregabalin (Lyrica - Pfizer), will be marketed soon and will be reviewed in the next issue of The Medical Letter.