Antidepressant effect of repetitive transcranial magnetic stimulation is not impaired by intake of lithium or antiepileptic drugs

Abstract

Introduction The effect of concomitant medication on repetitive transcranial magnetic stimulation (rTMS) outcomes in depression remains understudied. Recent analyses show attenuation of rTMS effects by antipsychotic medication and benzodiazepines, but data on the effects of antiepileptic drugs and lithium used as mood stabilizers or augmenting agents are sparse despite clinical relevance. Preclinical electrophysiological studies suggest relevant impact of the medication on treatment, but this might not translate into clinical practice. We aimed to investigate the role of lithium (Li), lamotrigine (LTG) and valproic acid (VPA) by analyzing rTMS treatment outcomes in depressed patients. Methods 299 patients with uni- and bipolar depression treated with rTMS were selected for analysis in respect to intake of lithium, lamotrigine and valproic acid. The majority (n = 251) were treated with high-frequency (10–20 Hz) rTMS of the lDLPFC for an average of 17 treatment sessions with a figure-of-8 coil with a MagVenture system aiming for 110% resting motor threshold, and smaller groups of patients were being treated with other protocols including intermittent theta-burst stimulation and bilateral prefrontal and medial prefrontal protocols. For group comparisons, we used analysis of variance with the between-subjects factor group or Chi-Square Test of Independence depending on the scales of measurement. For post-hoc tests, we used least significant difference (LSD). For differences in treatment effects between groups, we used an ANOVA with the between-subjects factor group (groups: no mood stabilizer, Li, LTG, VPA, Li + LTG) the within-subjects factor treatment (pre vs. post treatment with rTMS) and also Chi-Square Tests of independence for response and remission. Results Overall, patients showed an amelioration of symptoms with no significant differences for the main effect of group and for the interaction effect treatment by group. Based on direct comparisons between the single groups taking mood stabilizers against the group taking no mood stabilizers, we see a superior effect of lamotrigine, valproic acid and combination of lithium and lamotrigine for the response and remission rates. Motor threshold was significantly and markedly higher for patients taking valproic acid. Conclusion Being treated with lithium, lamotrigine and valproic acid had no relevant influence on rTMS treatment outcome. The results suggest there is no reason for clinicians to withhold or withdraw these types of medication from patients who are about to undergo a course of rTMS. Prospective controlled work on the subject is encouraged.

Accelerated theta burst stimulation for the treatment of depression: A randomised controlled trial

“…Further, although non-antidepressant concomitant medications were noted in a binary fashion (Table 3), we did not collate more detailed data such as the type of mood stabiliser medication (lithium or anticonvulsant mood stabilisers), concomitant benzodiazepine administration or the doses and treatment durations of these medications. This omission may be of relevance given these medications' possible influences on cortical excitability and therefore rTMS response [88,89], and in view of the literature that emerged since this study's conceptualisation that discuss the impact concomitant benzodiazepines might have on antidepressant response to rTMS [90e92]. Additionally, we did not systematically record tolerability issues expected with rTMS therapy, eg.…”

Effectiveness of Repetitive Transcranial Magnetic Stimulation in the Treatment of Bipolar Disorder in Comparison to the Treatment of Unipolar Depression in a Naturalistic Setting

“…Increased use of mood stabilizers in the group with bipolar depression was anticipated due to their common use in this patient population. Previous work has shown that intake of these medications aswell as that of lithium is not associated with inferior treatment outcomes in the naturalistic setting, providing evidence against the theoretical concern that drugs with an anticonvulsive mechanism of action might hamper with rTMS effects [20]. The less widespread use of SNRIs in the group of bipolar patients might be associated with concerns of increased risk of inducing mania.…”

“…We have reported previously on patients of this cohort with regards to rTMS outcomes, however with a then different and/or smaller samples and different objectives [16][17][18][19][20].…”

A Pilot Study of High-Frequency Transcranial Magnetic Stimulation for Bipolar Depression

“…31 An interpretation of these studies may be that quetiapine blunts the effects of rTMS, such that antipsychotics as a class may act as a moderator toward treatment responsiveness as suggested by others 32 ; meanwhile, mood stabilizers and antiepileptic drugs commonly used in difficult-to-treat mood disorders, including bipolar disorder, are not suggested to impinge on treatment effect of rTMS. 33 Moreover, sequential bilateral rTMS fails to achieve superiority to unilateral treatment, and given the established efficacy unilateral stimulation offers, efforts to optimize unilateral rTMS serve as a useful heuristic platform to begin to build from.…”