Abstract
In a recent study published in this journal (Rohde et al., 2020), we reported a 54% reduction in incidents of intentional self-harm/suicide attempts after initiation of methylphenidate in patients with unipolar depression. This finding suggests that individuals with other mental disorders that are frequently accompanied by intentional self-harm/suicide attempts may also benefit from methylphenidate. Therefore, we went on to evaluate whether this protective effect could also be observed among patients with schizophrenia, bipolar disorder and personality disorders. We included patients with attention deficit hyperactivity disorder (ADHD) as ‘positive controls’ due to the well-known efficacy of methylphenidate in the treatment of ADHD (Cortese et al., 2018).
The method employed was analogous to that used in our recent study on the effect of methylphenidate on unipolar depression (Rohde et al., 2020) and is described in detail in the Supplementary Material. In brief, via the Danish nationwide registers, we identified patients with schizophrenia, bipolar disorder, personality disorder and ADHD who redeemed their first prescription for methylphenidate (when aged 18 years or above). Subsequently, we employed a mirror-image design by comparing incidents of intentional self-harm/suicide attempts in the 2-year period leading up to the first redemption of a prescription for methylphenidate (the pre-mirror period) to the 2-year period following the redemption (the post-mirror period). Afterwards, we compared incidents of intentional self-harm/suicide attempts in the 2-year period leading up to discontinuation of treatment with methylphenidate to the 2-year period following the discontinuation (reverse mirror-image). To test whether the results of this study were confounded by co-prescription of methylphenidate and antidepressants, we examined whether there were differences in the number of patients using antidepressants before and after the first redemption of a prescription for methylphenidate.
We identified 535 individuals with schizophrenia, 421 with bipolar disorder, 3280 with personality disorder and 3044 with ADHD, who redeemed at least one prescription for methylphenidate. The results of the mirror analysis are shown in Table 1.
Incidents of self-harm or suicide attempts before and after initiation (mirror-image model) and discontinuation (reverse mirror-image model) of methylphenidate treatment among individuals with schizophrenia, bipolar disorder, personality disorder and ADHD.
ADHD: attention deficit hyperactivity disorder. X: small numbers that – according to Danish legislation – cannot be reported due to risk of identification.
No statistically significant change in the number of incidents of intentional self-harm/suicide attempts was found for schizophrenia (+3 events, increase of 16%, p = 0.77). A statistically significant reduction in the number of incidents of intentional self-harm/suicide attempts was found for individuals with bipolar disorder, personality disorder and ADHD, with a reduction of 9 events (75%, p = 0.03), 72 events (57%, p < 0.01) and 32 events (52%, p < 0.01), respectively (Table 1). When excluding individuals who also had a diagnosis of ADHD from the analyses (note: this reduces the statistical power of these analyses substantially), the only statistically significant reduction in intentional self-harm/suicide attempts was found among the individuals with personality disorder (Table 1). After discontinuation of methylphenidate treatment, the change in the number of incidents of self-harm/suicide attempts was not statistically significant for any of the diagnostic groups (Table 1).
Among the individuals with bipolar disorder, 261 patients used antidepressants before methylphenidate initiation compared to 261 patients after methylphenidate initiation (p = 1.00). Among the individuals with personality disorder, 1753 used antidepressants before methylphenidate exposure compared to 1668 after methylphenidate initiation (p < 0.01). Among the individuals with ADHD, 1130 individuals used antidepressants before methylphenidate initiation compared to 1042 after methylphenidate initiation (p < 0.01).
In this mirror-image study comparing the period leading up to methylphenidate initiation to the period following it, we found statistically significant reductions in intentional self-harm/suicide attempts upon methylphenidate initiation among individuals with bipolar disorder (75% reduction), personality disorder (57% reduction) and ADHD (52% reduction), but not in schizophrenia. These findings do not seem to be explained by antidepressant co-prescribed with methylphenidate as the proportion of individuals redeeming a prescription for an antidepressant in the pre- and post-mirror periods was largely similar. While it is well established that methylphenidate is associated with reduced suicidal ideation and behaviour in individuals with ADHD (Krinzinger et al., 2019), the reduced incidence of self-harm/suicide attempts after methylphenidate initiation in individuals with bipolar disorder and personality disorder observed in this study, and as recently reported also in depression (Rohde et al., 2020), represents largely unprecedented findings. Given the paucity of evidence-based treatments to prevent self-harm and the substantial prevalence of self-harm in these mental disorders, these findings are of clinical interest and suggest that (randomized) clinical studies of this phenomenon may be warranted.
With regard to a potential mechanism explaining the findings of this study, clinical studies of ADHD have shown that methylphenidate reduces impulsivity and emotional dysregulation (Suzer Gamli and Tahiroglu, 2018), which likely leads to less suicidal ideation and self-harm. Impulsivity and emotional dysregulation are commonly seen in other mental disorders as well – especially in relation to those where we have observed what appears to be a protective effect of methylphenidate on self-harm/suicide attempts – namely, unipolar depression (Rohde et al., 2020), bipolar disorder and personality disorder. Indeed, increased impulsivity has been linked to a higher risk of suicidal acts among individuals with borderline personality disorder (Soloff et al., 1994).
The key limitation of this study (see the Supplementary Material for a description of further limitations) as well as the analogue study of unipolar depression (Rohde et al., 2020) is their observational nature, which sets obvious limits for causal inference. Therefore, the suggested beneficial effect of methylphenidate on the risk of intentional self-harm/suicide attempts in unipolar depression, bipolar disorder and personality disorder – observed in our register-based studies – calls for randomized controlled trials.
Supplemental Material
sj-pdf-1-anp-10.1177_0004867421998779 – Supplemental material for Use of methylphenidate and the incidence of intentional self-harm or suicide attempts among individuals with schizophrenia, bipolar disorder and personality disorder
Supplemental material, sj-pdf-1-anp-10.1177_0004867421998779 for Use of methylphenidate and the incidence of intentional self-harm or suicide attempts among individuals with schizophrenia, bipolar disorder and personality disorder by Christopher Rohde, Estela Salagre, Jimmi Nielsen and Søren D Østergaard in Australian & New Zealand Journal of Psychiatry
Footnotes
Declaration of Conflicting Interests
The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Funding
The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: C.R. has received grants from the Lundbeck Foundation and the Novo Nordisk Foundation. S.D.Ø. has received grants from the Lundbeck Foundation, The Novo Nordisk Foundation, The Danish Cancer Society and Independent Research Fund Denmark.
Supplemental Material
Supplemental material for this article is available online.
References
Supplementary Material
Please find the following supplemental material available below.
For Open Access articles published under a Creative Commons License, all supplemental material carries the same license as the article it is associated with.
For non-Open Access articles published, all supplemental material carries a non-exclusive license, and permission requests for re-use of supplemental material or any part of supplemental material shall be sent directly to the copyright owner as specified in the copyright notice associated with the article.
