Certain drugs used to treat severe dermatologic diseases can have various neuropsychiatric adverse effects. Generating awareness of potential neuropsychiatric adverse events of these drugs is important because, while many of them may be mild and reversible, others can be more serious, sometimes permanent, and potentially fatal.
The most serious reactions are found with psoriasis drugs, especially non-biologic medications such as cyclosporine A and methotrexate, according to a recent review.1 “Given the number of systemic dermatologic therapies and the wide variety of their neurological and neuropsychiatric adverse effects, neurologists, psychiatrists, dermatologists, oncologists, and primary care providers must be aware of recorded neuropsychiatric adverse reactions,” wrote first author Melinda Liu, MD, of Baylor College of Medicine in Houston, Texas, and colleagues. “Prescribers should provide information about such adverse effects, offer methods for monitoring for them, particularly during the early months of treatment, and remain aware of the potential need to discontinue the medication,” the authors advised.
The following is a brief overview of drugs discussed in the article. The review includes a range of studies, from randomized controlled trials to case reports. It covers FDA-approved medications for dermatologic diseases that usually require systemic medications.
FDA-approved psoriasis drugs
Cyclosporin A. Neuropsychiatric adverse effects are dose- and duration-dependent. Treatment for over one year is strongly discouraged. Neurological adverse effects occur in up to 40% of patients, and many are reversible with treatment cessation. Headaches, paresthesias, and tremors are most common. Posterior reversible encephalopathy syndrome (PRES), a rare but serious (though reversible) condition which may involve the following:
• vision loss
Other rare neurological adverse events that have been reported include:
• progressive multifocal leukoencephalopathy (PML)
• cerebellar syndrome
• drug-induced Parkinsonism
Acitretin. Neurological adverse effects include idiopathic intracranial hypertension (IIH) and peripheral neuropathy. The drug should be avoided with statins, corticosteroids, colchicine and penicillamine due to neurological and muscular adverse events.
Due to reports of IIH with retinoids (isotretinoin, acitretin), tetracyclines (see below), and cyclosporin A (see below), these drugs should not be co-administered as they may incur possible additive risk. It should be noted that women are at increased risk of IIH.
Methotrexate. Cases of psychosis and mania, as well as leukoencephalopathy, have been reported. To decrease toxicity, concurrent folate administration, strict adherence to contraindications, and regular assessment of kidney and liver function is advised.
Apremilast. Dose-dependent adverse events are usually self-limited and mild to moderate. There have been some reports of depressed mood, but the quality of the evidence is questionable.
FDA-approved biologics for psoriasis
Tumor necrosis factor α-inhibitors. The use of TNFα inhibitors (eg, infliximab, etanercept, adalimumab) has in some cases resulted in psychosis, mania, optic neuritis, transverse myelitis, Guillain-Barre syndrome, and chronic inflammatory demyelinating polyneuropathy (CIDP). Because of rare reports that the drug may promote demyelinating disorders, the American Academy of Dermatology recommends avoiding TNFα-inhibitors in patients with a personal or family history of demyelinating disorders.
Interleukin inhibitors. There have been case reports of PRES with long-term ustekinumab but not secukinumab from medications such as ustekinumab, secukinumab, and ixekizumab. There is some concern for depression with ixekizumab.
FDA-approved autoimmune skin disease drugs
Corticosteroids. Used for treating autoimmune bullous diseases, SLE-related skin disorders, and atopic dermatitis, corticosteroids have been linked to neuropsychiatric disorders. These disorders are dose-dependent, with doses of 40 mg and above strongly linked to such disorders. Women are up to 6 times more likely to experience these disorders than men.
1. Liu M, Huang YY, Hsu S, Kass JS. Neurological and Neuropsychiatric Adverse Effects of Dermatologic Medications. CNS Drugs. 2016;30:1149-1168.