Myth: Psoriasis treatments may cause depression
It has been well documented that patients with inflammatory diseases such as psoriasis have an increased risk for depression. One population-based cohort study in the United Kingdom reported the risk of depression was greater in patients with severe psoriasis versus mild psoriasis. Younger psoriasis patients also had a higher risk compared to older patients. A US population-based study also reported that psoriasis was associated with major depression, but the severity of psoriasis and patient's age were unrelated. Therefore, all psoriasis patients may be at risk.
But are some therapies associated with an increased risk of depression? Increased concentrations of proinflammatory cytokines such as tumor necrosis factor α have been associated with depression apart from psoriasis. Administering immunomodulating agents has been shown to increase the risk of depression.
Depression has been cited as an adverse effect of apremilast in the drug's package insert, which states, "Before using [apremilast] in patients with a history of depression and/or suicidal thoughts or behavior prescribers should carefully weigh the risks and benefits of treatment." In clinical trials, 1.3% (12/920) of participants treated with apremilast reported depression compared to 0.4% (2/506) treated with placebo. Dermatologists should remain vigilant about monitoring for symptoms of depression in patients treated with apremilast.
However, depression in the context of autoimmune disorders or any disorder with increased inflammation has responded to treatment with tumor necrosis factor α antagonists. The relationship between depression and inflammation suggests that there is an inflammatory subtype of depression and use of anti-inflammatory agents may treat both inflammation and depression.
Disease control has been shown to improve symptoms of depression in psoriasis patients. A study of 618 patients with moderate to severe psoriasis who were treated with etanercept or placebo for 12 weeks revealed that more patients receiving etanercept experienced 50% improvement in 2 rating scales of depression compared to placebo.
Excessive worrying, a form of psychological distress, can impact treatment outcomes in patients with psoriasis. A 2003 study found that patients with psoriasis who are classified as high-level worriers may benefit from adjunctive psychological intervention before and during treatment. In this cohort of psoriasis patients receiving psoralen plus UVA (PUVA) therapy, high-level worry was the only significant predictor of time taken for PUVA to clear psoriasis (P=.01). Patients in the high-level worry group cleared with PUVA treatment at a rate of 1.8 times slower than the low-level worry group.
In conclusion, psoriasis patients should follow the treatment plan outlined by dermatologists, as improving psoriasis symptoms may help alleviate depression or prevent it from occurring. Patients with a history of depression should be monitored carefully by dermatologists or referred to another health care professional, and patients as well as family and friends should be encouraged to report any depression symptoms.
The prescribing information for apremilast lists a warning (but not a black-box warning) for depression. Long-term registries will determine if there is truly an increased risk of depression when taking apremilast. When I counsel patients before prescribing apremilast, I mention this potential increased risk of depression as noted in the prescribing information, but I tell them that the risk is very low and that a true risk has not yet been determined in long-term registries. I mention to patients that if they really do feel depressed after starting apremilast, they should stop taking apremilast and contact me.
Long-term registries for etanercept, adalimumab, infliximab, and ustekinumab do not indicate an increased risk for depression. Intuitively, if a patient with severe psoriasis has depression worsened by their psoriasis, it stands to reason that improving their skin will likely improve their mood, which clinical trials have shown using patient-related outcomes.
—Jashin J. Wu, MD (Los Angeles, California)