Association of Optimal Lamotrigine Serum Levels and Therapeutic Efficacy in Mood Disorders

Kumar, Rakesh; Núñez, Nicolás A.; Prokop, Larry J.; Veldić, Marin; Betcher, Hannah K.; Singh, Balwinder

doi:10.1097/jcp.0000000000001475

Cited by 7 publications

(11 citation statements)

References 28 publications

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“…21 Serum levels of LTG would be needed for the accurate examination of the efficacy of LTG. 22 In addition, the rash was not diagnosed by a dermatologist in this study, and causes other than LTG were not excluded, which may have led to overdiagnosis. 23 Furthermore, the definition of slow titration used in this study is comprehensive, and schedules with fewer initial doses that used the standard titration interval could not be distinguished from those that used prolonged intervals with the standard titration dosing.…”

Section: Limitationsmentioning

confidence: 89%

Impact of Selected Initial Titration Schedules on Safety and Long-Term Effectiveness of Lamotrigine for the Treatment of Mood Disorders

Nakamura

Tomita²,

Hirota³

et al. 2022

J Clin Psychopharmacol

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PurposeLamotrigine (LTG) is used for treatment of mood disorders, but it is associated with the risk of rash occurrence in the initial administration phase. Although slow titration reduces this risk, its effectiveness in the treatment of mood disorders has not been verified. The effects of titration method on the safety and effectiveness of LTG for the treatment of mood disorders were examined in this study.MethodsThis retrospective cohort study included 312 patients with mood disorders who underwent initiation of LTG therapy. Data regarding baseline demographics, titration schedules, concomitant medications, and time to and cause of discontinuation of LTG were collected. A multivariate analysis was used to evaluate the effects of the titration schedules. The 12-month effectiveness was also evaluated.ResultsThe 12-month discontinuation rate of LTG was 16.7%. The most frequent cause of discontinuation was development of a rash (47.7%, n = 312). Fast titration (adjusted odds ratio, 8.15) significantly increased the risk of rash development, and slow titration (adjusted odds ratio, 0.29) significantly decreased this risk. The time to all-cause discontinuation was not significantly different between the slow and standard titration groups (n = 303). After 12 months of treatment, the condition of 46.7% patients were rated much or very much improved using CGI-C.ConclusionsAlthough slow titration of LTG reduces the occurrence of a rash, it is not more effective than standard titration in the long term. Optimizing the initial LTG titration schedule for patients with mood disorders is challenging.

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Section: Limitationsmentioning

confidence: 89%

Impact of Selected Initial Titration Schedules on Safety and Long-Term Effectiveness of Lamotrigine for the Treatment of Mood Disorders

Nakamura

Tomita²,

Hirota³

et al. 2022

J Clin Psychopharmacol

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“…Monitoring for adverse effects needs to include baseline and periodic assessment for symptoms and signs of thyrotoxicosis (palpitations/tachycardia, hand tremors, anxiety, insomnia, unintentional weight loss, oligo/amenorrhea, fragility fractures/low bone density) [ 21 ]. Long-term supratherapeutic TH augmentation, especially in postmenopausal women with reduced physical activity, a personal history of cigarette smoking, an excessive history of serotonergic antidepressant exposure, a family history of osteoporosis, and advanced age is associated with high risk for fragility fractures and osteoporosis [ 27 ]. T4 is often started at 50 mcg per day and optimized to 100–150 mcg per day [ 21 ].…”

Section: Discussionmentioning

confidence: 99%

“…The risk of bias was assessed for random sequence generation, allocation concealment, the blinding of participants and personnel, the blinding of outcome assessment, incomplete outcome data, selective reporting, and other biases. For open-label non-randomized studies/observation studies, we used the Methodological Index for Non-Randomized Studies [ 26 , 27 ]. Quantitative tests to assess publication bias were not performed due to the limited number of studies.…”

Section: Methodsmentioning

confidence: 99%

Thyroid Hormone Augmentation for Bipolar Disorder: A Systematic Review

et al. 2022

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Thyroid hormone (TH) augmentation, although commonly used for major depression, is sparingly used for bipolar disorder (BD) after the failure of mood-stabilizing agents. While the exact mechanisms of thyroid hormone action in BD remains unclear, central thyroid hormone deficit has been postulated as a mechanism for rapid cycling. This systematic review—conducted in accordance with the PRISMA guidelines—of eight studies synthesizes the evidence for TH augmentation in BD. A systematic search of the Ovid MEDLINE, Embase, PsycINFO, and Cochrane databases was conducted for randomized controlled trials (RCT), open-label trials, and observational studies of levothyroxine (LT4) and triiodothyronine (T3) for BD. Open-label studies of high dose LT4 augmentation for bipolar depression and rapid cycling showed improvement in depression outcomes and reduction in recurrence, respectively. However, an RCT of high-dose LT4 did not show benefit in contrast to placebo. An RCT comparing LT4, T3, and placebo showed benefit only in rapid-cycling bipolar women. A meta-analysis could not be completed due to significant differences in study designs, interventions, and outcomes. Our systematic review shows mixed evidence and a lack of high-quality studies. The initial promise of supratherapeutic LT4 augmentation from open-label trials has not been consistently replicated in RCTs. Limited data are available for T3. The studies did not report thyrotoxicosis, and TH augmentation were well tolerated. Therefore, TH augmentation, especially with supratherapeutic doses, should be reserved for highly treatment-resistant bipolar depression and rapid-cycling BD.

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“…A systematic review conducted in an adult population underscored the clinical recommendation for using LAM serum levels to target clinical efficacy in adult mood disorders. This review suggested that it is reasonable to obtain serum levels for LAM and consider an optimization to a minimum level of 3 μg/mL (0.003 kg/m 3 ) of LAM in adults 25 …”

Section: Discussionmentioning

confidence: 99%

“…This review suggested that it is reasonable to obtain serum levels for LAM and consider an optimization to a minimum level of 3 μg/mL (0.003 kg/m 3 ) of LAM in adults. 25 To date, no study has been conducted to review the evidence for effective serum levels of LAM treatment of PMD. Therefore, future RCTs should consider including therapeutic drug monitoring in PMD.…”

Section: Discussionmentioning

confidence: 99%

Efficacy and safety of lamotrigine in pediatric mood disorders: A systematic review

Kumar

Garzon

Yuruk

et al. 2022

Acta Psychiatr Scand

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Aim To appraise the current evidence on the efficacy and safety of lamotrigine (LAM) in the treatment of pediatric mood disorders (PMD) (i.e., Major Depressive disorder [MDD], bipolar disorder [BD]). Methods Major databases were searched for randomized controlled trials (RCTs), open‐label trials, and observational studies reporting on pediatric (age < 18 years) patients treated with LAM for mood disorders. Results A total of 3061 abstracts were screened and seven articles were selected for inclusion. Seven studies (319 BD and 43 MDD patients), including one RCT (n = 173), three prospective (n = 105), and three retrospective (n = 84) studies, met the study criteria with a study duration range from 8 to 60.9 weeks. The mean age of this pooled data is 14.6 ± 2.0 years. LAM daily dosage varied from 12.5 to 391.3 mg/day among the studies. In an important finding, the RCT reported favorable outcomes with LAM (HR = 0.46; p = 0.02) in 13‐ to 17‐year‐old age group as compared with 10‐ to 12‐year‐old age group (HR = 0.93; p = 0.88). In addition, time to occurrence of a bipolar event trended toward favoring LAM over placebo. All the studies identified LAM as an effective and safe drug in PMDs especially, BDs. Overall, LAM was well tolerated with no major significant side effects and no cases of Stevens–Johnson syndrome. Conclusions Most studies suggested that LAM was safe and effective in pediatric patients with mood disorders. However, the data regarding the therapeutic range for LAM are lacking. Based on the data, there is inconsistent evidence to make conclusive recommendations on therapeutic LAM dosage for mood improvement in the pediatric population. Further studies including larger sample sizes are required to address this relevant clinical question.

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Association of Optimal Lamotrigine Serum Levels and Therapeutic Efficacy in Mood Disorders

Cited by 7 publications

References 28 publications

Impact of Selected Initial Titration Schedules on Safety and Long-Term Effectiveness of Lamotrigine for the Treatment of Mood Disorders

Impact of Selected Initial Titration Schedules on Safety and Long-Term Effectiveness of Lamotrigine for the Treatment of Mood Disorders

Thyroid Hormone Augmentation for Bipolar Disorder: A Systematic Review

Efficacy and safety of lamotrigine in pediatric mood disorders: A systematic review

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