General practice database on mortality in adults on methylphenidate: cohort study.

OBJECTIVES: Methylphenidate is a 'prescription only' drug against attention disorders which is increasingly used by adults. We investigated whether methylphenidate in adults was associated with an increased risk of psychiatric events such as depression, and suicide attempt and overall mortality. DESIGN: A population-based matched cohort design. SETTING: The Integrated Primary Care Information system, a general practitioners (GP) database in the Netherlands with a source population of 2.5 million inhabitants. PARTICIPANTS: During the study period between 1 June 1996 and 1 January 2018, 8905 adults started methylphenidate and were matched to 10 non-users on sex, age, GP practice and ad prescription date. The total study population consisted of 97 198 participants. MAIN OUTCOME MEASURES: Serious psychiatric events such as depression and suicide attempts, and overall mortality. ANALYSES: Risks of development of each event during the use of methylphenidate were expressed as HR with 95% CI, adjusted for relevant confounders with methylphenidate as a time-dependent determinant. Additional adjustment was performed for the intervention ('intention-to-treat'). RESULTS: Although during follow-up, the unadjusted risks of depression and suicide attempt were strongly increased in users, depression and psychosis became non-significant after adjustment for alcohol-abuse and substance-abuse and psychiatric disease in the medical history and after adjustment for 'intention-to-treat'. However, the risk of suicide attempts remained significantly increased after full adjustment (HR 2.0; 95% CI 1.1 to 3.6), and was highest in women and in participants within the age-group of 18-40 years. The unadjusted risk of overall mortality was strongly increased, but this lowered to a significant 30% risk increase (HR 1.3; 95% CI 1.1 to 1.6) after full adjustment. CONCLUSION: There is an increased risk of suicide attempts in adults up to 40 years of age after starting methylphenidate and this risk should be carefully considered before prescribing to this group.

Methylphenidate Treatment Adherence and Persistence in Children in the Netherlands.

Objectives: Numerous studies have examined determinants contributing to methylphenidate adherence and persistence, but these were mainly conducted in adults. These determinants are likely to be different in children as they usually rely on their parents to provide them with the care they need. The objective was to study child and family characteristics as determinants of methylphenidate adherence and persistence in children. Methods: The study population consists of 307 children from the Generation R Study in the Netherlands, who had at least one dispensing record of methylphenidate until the age of 16 years. Adherence was defined as a medication possession ratio ≥0.80 up to 2 years after treatment initiation. Persistence was defined as the duration of treatment until a discontinuation period of ≥6 months. Family and child characteristics were tested as determinants of adherence with multivariable logistic regression analysis. Persistence was evaluated using a Kaplan-Meier analysis. Results: Children of mothers with one child (adjusted odds ratio [OR]: 2.31, 95% confidence interval [CI]: 1.17-4.54) or of mothers with an average household income (compared to high) were more likely to be adherent (adjusted OR: 3.45, 95% CI: 1.43-8.31). Children who started treatment at the age of 12-16 years (compared to <12 years) (adjusted hazard ratio [HR]: 3.55, 95% CI: 2.54-4.98) and girls (adjusted HR: 1.44, 95% CI: 1.07-1.95) were more often nonpersistent. Conclusion: Both child and family characteristics may play a role in methylphenidate treatment adherence. Furthermore, gender and the start age of treatment were found to be associated with nonpersistence. These findings may be important for health care professionals when initiating methylphenidate treatment in children.

Methylphenidate Treatment Initiated During Childhood Is Continued in Adulthood in Half of the Study Population.

Objectives: To estimate the number of patients who started methylphenidate during childhood and continued treatment beyond the age of 18 years and to study the determinants that may be associated with continuing treatment. Methods: Patients 17 years of age and younger who have received at least one prescription of methylphenidate were identified in the Integrated Primary Care Information database (1996-2017). Logistic regression analyses were performed to assess the association between potential determinants and continuation with methylphenidate treatment at the age of 18 years. Results: Fifty-three percent of all methylphenidate users (n = 1020) continued their treatment after the age of 18 years. Patients were more likely to continue treatment with methylphenidate if they started treatment at the age of 15-17 years compared with patients of 11 years and younger (adjusted odds ratio [OR]: 5.74, 95% confidence interval [CI]: 1.48-22.31), if they had a medication possession ratio (MPR) between 0.80 and 1.00 compared with a low MPR (adjusted OR: 2.18, 95% CI: 1.23-3.85) and if they lived in an area with a medium level of urbanization (adjusted OR: 1.98, 95% CI: 1.06-3.69). Furthermore, a relatively high number of patients had a MPR >1.0 (24.8%), of whom 91.3% started their treatment when they were between 15 and 17 years of age. Conclusions: Methylphenidate treatment initiated during childhood was continued in half of the study population when reaching the age of 18, where adolescents were more likely to continue treatment than young children. We also found that ∼25% of our study population had a MPR >1, mainly patients 15-17 years of age, which may suggest misuse or abuse of methylphenidate.

Treatment Satisfaction of Patients With Advanced Non-Small-cell Lung Cancer Receiving Platinum-based Chemotherapy: Results From a Prospective Cohort Study (PERSONAL).

INTRODUCTION: In patients with advanced non-small-cell lung cancer, the treatment benefits and risks need to be constantly weighed. We explored patient-reported satisfaction with therapy (SWT) and assessed its value in addition to quality of life (QoL) and adverse events (AEs). PATIENTS AND METHODS: In a prospective multicenter cohort study, patients with stage IIIB/IV non-small-cell lung cancer received platinum-pemetrexed chemotherapy. They completed the World Health Organization Quality of Life-BREF (WHOQoL-BREF) and European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) before and during chemotherapy. After the last cycle, patients reported on SWT, expectations of therapy, and feelings about side effects (FSE) using the Cancer Therapy Satisfaction Questionnaire. The explained variance (R2) of QoL after treatment by SWT was calculated. Using multivariable linear regression, we examined the association of SWT with patient- and treatment-related variables, FSE, and AEs. RESULTS: Eighty-nine patients finished 4 cycles of chemotherapy, 65 of whom completed the Cancer Therapy Satisfaction Questionnaire. Fifty-six patients (86.2%) would probably or definitely decide to undergo the same treatment again, regardless of deterioration or improvement in QoL or a high or low frequency of AEs during chemotherapy. The explained variance of QoL by SWT was greatest for the EORTC QLQ C-30 global health status/QoL scale (R2 = 0.170). Patient age (ß = 0.43; 95% confidence interval [CI], 0.05-0.82), FSE (ß = 0.17; 95% CI, 0.06-0.29), and tumor response (ß = 7.93; 95% CI (1.64 to 14.22)) were independently associated with SWT. CONCLUSION: SWT could provide important supplementary information in addition to QoL assessments and treatment toxicities. Tumor response, older age, and FSE score were associated with better SWT. These insights could affect decision-making during palliative chemotherapy.

Antidepressant use and the risk of suicide: a population-based cohort study.

BACKGROUND: The existing literature provides contradictory evidence on antidepressant use and risk of suicide. Some studies have shown that the use of Selective Serotonin Reuptake Inhibitors (SSRIs) is associated with an increased risk of suicide, especially during the first months of treatment, whereas other studies did not confirm this association. For this reason, our objective was to investigate the association between antidepressant use and risk of suicide in incident antidepressant users in relation to time since starting therapy. METHODS: We conducted a population-based cohort study within the Dutch Integrated Primary Care Information (IPCI) database, in incident users of antidepressant therapy between 1994 and 2012 (n=27,712). Cox proportional hazard models were used to study the association between current use of SSRIs, tricyclic antidepressants (TCA) and other antidepressants and risk of suicide or attempted suicide. RESULTS: During follow-up, a total of 280 incident antidepressant users attempted or committed suicide. Current use of SSRIs (hazard ratio (HR): 0.78, 95% CI: 0.57-1.07), TCAs (HR: 0.82, 95% CI: 0.48-1.42) or other antidepressants (HR: 0.75, 95% CI: 0.47-1.18) was not statistically significantly associated with suicide compared to past use of any of the antidepressants. LIMITATIONS: Although a large healthcare database was used, the number of reported cases of suicide (attempt) was low. CONCLUSIONS: This study did not indicate an increase in risk of suicide after starting treatment with SSRIs, TCAs or other antidepressants compared with past antidepressant use.