After the FDA put the more strict iPLEDGE program in place for the companies marketing the drug in the US, in 2011, 155 pregnancies occurred among 129,544 women of childbearing potential taking isotrentinoin (0.12%).People taking isotretinoin are not permitted to donate blood during and for at least one month after discontinuation of therapy due to its teratogenicity. Psychological effects
Rare psychological side effects may include depression, worsening of pre-existing depression, aggressive tendencies, irritable mood and anxiety. Very rare effects include abnormal behaviour, psychosis, suicidal ideation, suicide attempts and suicide. In a total of 5577 adverse reactions reported to the UKs MHRA up to 31 March 2017, the plurality (1207, or 22%) concerned psychiatric effects. There were 85 reports of suicidal ideation, 56 of suicide and 43 of suicide attempts.The association between isotretinoin use and psychopathology has been controversial. Beginning in 1983, isolated case reports emerged suggesting mood change, particularly depression, occurring during or soon after isotretinoin use. A number of studies have been conducted since then of the drugs effect on depression, psychosis, suicidal thoughts and other psychological effects. Depression and suicidality
Isotretinoin is the only non-psychiatric drug on the FDAs top 10 list of drugs associated with depression and is also within the top 10 for suicide attempts. A black box warning for suicide, depression and psychosis has been present on isotretinoins packaging in the United States since 2005.
Psychosis
Isotretinoin has also been linked to psychosis. Many of the side effects of isotretinoin mimic hypervitaminosis A, which has been associated with psychotic symptoms. The dopamine hypothesis of schizophrenia and psychosis suggests that an increase in dopaminergic stimulation or sensitivity in the limbic system causes psychotic symptoms.It has been suggested that dysregulation of retinoid receptors by retinoids such as isotretinoin may cause schizophrenia. The evidence for this is threefold: transcriptional activation of the dopamine D2 receptor – in addition to serotonin and glutamate receptors – is regulated by retinoic acid; schizophrenia and the retinoid cascade have been linked to the same gene loci; and retinoid dysfunction causes congenital anomalies identical to those observed in people with schizophrenia. Further, the expression of dopamine receptors has indeed been shown to be regulated by retinoic acid. Musculoskeletal
Isotretinoin has a number of muscoloskeletal effects. Myalgia (muscular pain) and arthralgia (joint pain) are rare side effects. Retinoids, such as high dose etretinate, are well known to cause bone changes, the most common type of which is hyperostotic changes (excessive bone growth), especially in growing children and adolescents. Other problems include premature epiphyseal closure and calcification of tendons and ligaments. The bones of the spine and feet are most commonly affected. Risk factors for skeletal effects include older age, greater dosage and longer course of treatment. Most bone changes cause no symptoms and may only be noticed using X-ray imaging. Gastrointestinal
Isotretinoin may cause non-specific gastrointestinal symptoms including nausea, diarrhea and abdominal pain.