Ingenol mebutate, sold under the brand name Picato, is a substance that is found in the sap of the plant Euphorbia peplus, commonly known as milkweed, and is an inducer of cell death. A gel formulation of the drug has been approved by the U.S. Food and Drug Administration (FDA) and by the European Medicines Agency (EMA) for the topical treatment of actinic keratosis. Two different strengths of the gel have been approved for use on either the face and scalp (0.015%) or the trunk and extremities (0.05%), respectively. In 2020 the drug was withdrawn from the market in the EU. Adverse effects
Irritation of the application site is very common. The various types of irritation include redness, scaling, crusting, pain, severe itching, and sometimes infection. Additional possible side effects include eye irritation, such as periorbital edema (3% of patients in studies), headaches (2%) and nasopharyngitis (running nose, 2%).Allergic reactions, shingles, changes in pigmentation at application site, chemical conjunctivitis, and corneal burns may also occur.The European Medicines Agency recommended suspending the marketing authorisation of ingenol mebutate due to concerns regarding increased incidence of skin cancer in patients treated with topical ingenol mebutate compared to vehicle or imiquimod. Physicians were advised to refrain from prescribing ingenol and to use different treatment options. Subsequently, the marketing authorization holder requested withdrawal of the manufacturing authorization for commercial reasons. The withdrawal was granted and therefore, ingenol mebutate is no longer registered in the EU.
The first line of pharmacotherapy is usually SSRIs due to their purported more tolerable nature and reduced side effects compared to the irreversible monoamine oxidase inhibitors or tricyclic antidepressants. Studies have found that the mean response to antidepressant medications for people with dysthymia is 55%, compared with a 31% response rate to a placebo. The most commonly prescribed antidepressants/SSRIs for dysthymia are escitalopram, citalopram, sertraline, fluoxetine, paroxetine, and fluvoxamine. It often takes an average of 6–8 weeks before the patient begins to feel these medications therapeutic effects. Additionally, STAR*D, a multi-clinic governmental study, found that people with overall depression will generally need to try different brands of medication before finding one that works specifically for them. Research shows that 1 in 4 of those who switch medications get better results regardless of whether the second medication is an SSRI or some other type of antidepressant.In a meta-analytic study from 2005, it was found that SSRIs and TCAs are equally effective in treating dysthymia. They also found that MAOIs have a slight advantage over the use of other medication in treating this disorder. However, the author of this study cautions that MAOIs should not necessarily be the first line of defense in the treatment of dysthymia, as they are often less tolerable than their counterparts, such as SSRIs.Tentative evidence supports the use of amisulpride to treat dysthymia but with increased side effects. Combination treatment
When pharmacotherapy alone is compared with combined treatment with pharmacotherapy plus psychotherapy, there is a strong trend in favour of combined treatment.