Danger of antidepressant medications, response of the Committee.
Parliamentary Questions
WRITTEN QUESTION E-1975/03
Submission: Anna Karamanou (PSE) to the Commission
(03 June 2003)
Subject: Are widely available antidepressant medications dangerous for health?
E-1975/03EL
Response of Mr. Liikanen
on behalf of the Commission
(1.8.2003)
The regulatory authority of the United Kingdom for medicines and healthcare products [Medicines and Healthcare products Regulatory Agency (MHRA)] informed the Committee that there were new data from clinical trials of paroxetine (Seroxat) in children and adolescents at the end of May 2003. These new data were reviewed by a group of experts regarding SSRIs (selective serotonin reuptake inhibitors) and the Committee on the Safety of Medicines (CSM) of the European Medicines Evaluation Agency. The data do not show effectiveness regarding depression in the mentioned age group and indicate an increased risk of self-harm and possible suicidal tendencies in the Seroxat group compared to the placebo group. Various analyses show that the above risk is approximately 1.5 to 3.2 times greater with Seroxat compared to the placebo.
Based on the aforementioned data, the CSM recommended that Seroxat should not be used in children and adolescents under the age of 18 for the treatment of depression. Seroxat has not received authorization for use in this age group under 18, but it is used in this age group off-label when prescribers, at their own discretion, determine that it is the appropriate treatment for a specific patient.
The above recommendation was communicated to healthcare professionals via Public Health Link on June 10, 2003, and was included on the MHRA website along with information for patients. Revised patient information leaflets, which include the new recommendation, are being sent to prescribers and pharmacists.
This new warning to the pediatric sector raises concerns regarding the risk-benefit ratio of paroxetine. The United Kingdom believes that, in the interest of the Community, the risk-benefit ratio of paroxetine should be re-evaluated.
On June 12, 2003, the United Kingdom referred the issue to the Committee for Medicinal Products for Human Use (CPMP) of the European Medicines Evaluation Agency (EMEA), in accordance with Article 31 of Directive 2001/83/EC [1]. The issue was discussed at the CPMP meeting in June 2003, and the procedure was initiated.
The issue of the appearance of withdrawal syndrome and suicidal tendencies regarding Prozac (fluoxetine) was examined at the European level within the framework of the Committee for Medicinal Products for Human Use (CPMP) of the EMEA. This committee reached the following conclusions in September 2002:
“Based on the available information and the discussion within the committee, the CPMP considered that the benefit/risk ratio of Prozac is positive for use in major depressive episodes, obsessive-compulsive disorders, and as an adjunct to psychotherapy for psychogenic bulimia.”
The summary of product characteristics must include the following information:
“4.4 Special warnings and precautions for use”
Suicide:
Since improvement may not occur during the first few weeks of treatment, as with all antidepressants, patients should be closely monitored throughout this period. The possibility of suicidal attempts is inherent in depression, and this tendency may persist until significant remission occurs. According to general clinical experience with all depression treatments, the risk of suicide may increase in the early stages of recovery.
4.8 Adverse effects
Upon discontinuation of treatment, withdrawal symptoms have been reported in relation to SSRIs (selective serotonin reuptake inhibitors), although based on available evidence, it does not appear to be due to dependence. Common symptoms include dizziness, paresthesia, headache, anxiety, and nausea, most of which are mild and self-limiting.
Plasma concentrations of fluoxetine and norfluoxetine gradually decrease upon completion of treatment, which makes gradual dose reduction unnecessary for most patients.
4.2 Dosage and administration
According to the World Health Organization (WHO) consensus statement, the administration of antidepressant medications should continue for at least 6 months.
Children: The use of fluoxetine is not recommended in children and adolescents (under the age of 18), as the degree of safety and efficacy has not been established.
The above information is available on the EMEA website. (www.emea.eu.int)
The pharmacovigilance team of the scientific committee of the EMEA closely monitors all medications in the selective serotonin reuptake inhibitor (SSRI) class, including fluoxetine. In the past, in 2000, the CPMP agreed on essential safety warnings regarding SSRIs and withdrawal symptoms.
[1] Directive 2001/83/EC of the European Parliament and of the Council of November 6, 2001, on the Community code relating to medicinal products for human use, OJ L 311, 28.11.2001.