can you take seroquel with lamictal
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Lamotrigine
Lamotrigine, sold as the brand name Lamictal among others, is a medication used to treat epilepsy and stabilize mood in bipolar disorder. For epilepsy, this includes focal seizures, tonic-clonic seizures, and seizures in Lennox-Gastaut syndrome. In bipolar disorder, lamotrigine has not been shown to reliably treat acute depression; but for patients with bipolar disorder who are not currently symptomatic, it appears to be effective in reducing the risk of future episodes of depression.
Common side effects include nausea, sleepiness, headache, vomiting, trouble with coordination, and rash. Serious side effects include lack of red blood cells, increased risk of suicide, Stevens–Johnson syndrome, and allergic reactions. Concerns exist that use during pregnancy or breastfeeding may result in harm. Lamotrigine is a phenyltriazine, making it chemically different from other anticonvulsants. Its mechanism of action is not clear, but it appears to inhibit release of excitatory neurotransmitters via voltage-sensitive sodium channels and voltage-gated calcium channels in neurons.
1991
Lamotrigine was first marketed in the United Kingdom in 1991, and approved for use in the United States in 1994. It is on the World Health Organization’s List of Essential Medicines. In 2019, it was the 71st most commonly prescribed medication in the United States, with more than 10 million prescriptions.
For Bipolar Depression, Lamotrigine–Quetiapine Combination
Bipolar depression continues to be difficult to treat: Only quetiapine, fluoxetine–olanzapine combination, and lurasidone have shown unequivocal short-term efficacy. Evidence for benefit with lamotrigine has been mixed. Researchers conducted a 1-year, placebo-controlled study of the efficacy of adjunctive lamotrigine (200 mg/day) in 202 patients with bipolar depression (approximately 75% with bipolar disorder type I). All participants were taking quetiapine (150–300 mg/day).
The researchers also compared effects of folic acid, a possibly effective agent for depression, versus placebo in the study, which used a 2×2 factorial design and an adaptive randomization process to balance clinical factors between groups. Many patients were taking other medications, including lithium, valproate, and antidepressants in various combinations.
12 weeks
Self-reported depression symptoms were fewer with lamotrigine than with placebo at 52 weeks. Remission rates were greater in lamotrigine subjects at 12 weeks (31% vs. 16%) and 52 weeks (36% vs. 13%). Folic acid seemed to interfere with lamotrigine response at 12 weeks but not at 52 weeks. Clinically significant manic symptoms and additional treatments for mania did not differ between treatment groups.
CITATION(S):
Geddes JR et al. Comparative evaluation of quetiapine plus lamotrigine combination versus quetiapine monotherapy (and folic acid versus placebo) in bipolar depression (CEQUEL): A 2 × 2 factorial randomised trial.
Abstract
Background:
Lamotrigine and quetiapine are commonly used in bipolar disorder, but there are no published systematic studies of their use in combination for treatment-resistant bipolar depression.
Methods:
We studied 39 trials in outpatients (15 with bipolar I disorder, 22 with bipolar II disorder, and 1 with bipolar disorder not otherwise specified; 1 patient had 2 trials) with depression resistant to quetiapine or lamotrigine who were taking a mean of 1.7 other prescription psychotropic medications. Patients were given either open-label lamotrigine or quetiapine naturalistically, for up to 12 weeks of combination therapy.
Results:
Lamotrigine (mean dose, 204.2 mg/d) plus quetiapine (mean dose, 188.5 mg/d) increased the euthymia rate (0.0% to 46.2%), decreased syndromal (79.5% to 30.8%) and subsyndromal (20.5% to 15.4%) depression rates, and improved Clinical Global Impression-Severity (mean change, -1.0) and Global Assessment of Functioning (mean change, +5.9) scores. Approximately one-fifth of patients discontinued therapy (20.5%) or required subsequent additional pharmacotherapy (20.5%). Only 10.3% discontinued due to adverse effects, and there was no significant change in mean body weight.
Conclusions:
The findings of this uncontrolled open pilot study must be viewed with caution. However, randomized, double-blind, placebo-controlled studies are warranted to confirm the possibility that combination therapy with lamotrigine and quetiapine is effective and well tolerated in patients with treatment-resistant bipolar depression.
Methods
Data collection
Study data extracted from a routine therapeutic drug monitoring (TDM) service database at the Department of Clinical Pharmacology, Karolinska University Hospital and all patients subjected to analysis of quetiapine serum concentration identified. Serum quetiapine concentrations measured by a LC-MS method and lamotrigine by a HPLC method. Among the quetiapine-treated patients, individuals receiving co-treatment with lamotrigine identified by review of medication registered at the time of quetiapine analysis and by screening the above mentioned database for analyses of lamotrigine serum concentrations.
For each patient receiving co-medication with quetiapine and lamotrigine (case) a control patient subjected to quetiapine analysis and unexposed to lamotrigine identified. Cases and controls matched for gender, age (±5 years), quetiapine preparation (instant release or slow release) and dosage interval. Patients co-medicated with other drugs known to interact with quetiapine excluded.
Statistical analysis
To remove the potential influence of unequal sampling times, 12 h quetiapine concentrations imputed from each measured concentration. Twelve hours chosen since most samples (82%) where drawn approximately 12 h post-dose. For quetiapine instant release tablets, the imputation was based on an assumption of first-order elimination with a half-life of 7 h. At steady-state, the quetiapine concentration is relatively stable 10–16 h following administration of an extended release tablet.
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Hence, no imputation used for such samples. In accordance with published data, the concentration 12 h after intake of an extended release tablet assumed to be twice that of the concentration measured approximately 24 h post-dose. For each case and each control, a quetiapine concentration : dose (C : D) ratio calculated by dividing the measured quetiapine serum concentration (nmol l−1) by the daily oral quetiapine dose prescribed at the time of serum analysis (mg day−1). If more than one C : D ratio attainable in a single patient due to repeated testing, the median value of all available ratios used in the statistical analyses.
Wilcoxon
In the main analysis, quetiapine C : D ratios compared pair-wise between cases and matched controls using the Wilcoxon signed rank test. To validate the robustness of the results, data re-evaluated in a secondary analysis using the Mann-Whitney U-test. Unlike the paired test used in the main analysis, this unpaired test not dependent on the assumptions that each case and its matched control only differ with regard to lamotrigine exposure.
The potential influence of lamotrigine concentration on the strength of the proposed interaction investigated by means of Spearman rank correlation. In this analysis, the lamotrigine area under the concentration–time curve (AUC) in each case correlated to the quetiapine C : D ratio. The AUCs calculated from measured lamotrigine concentrations and sampling times, assuming first-order elimination with a half-life of 24 h.
Data extraction performed using Crystal Reports XI, Business Objects Software Ltd, and all statistical analyses performed using R 2.10.1.
WHAT IS LAMICTAL?
Lamictal (lamotrigine) an anticonvulsant used alone or in combination with other antiseizure medications for treating certain types of seizures.
WHAT IS SEROQUEL?
Seroquel a prescription medicine used to treat:
- schizophrenia in people 13 years of age or older
- bipolar disorder in adults, including:
- depressive episodes associated with bipolar disorder
- manic episodes associated with bipolar I disorder alone or with lithium or divalproex
- long-term treatment of bipolar I disorder with lithium or divalproex
- manic episodes associated with bipolar I disorder in children ages 10 to 17 years old
It not known if Seroquel is safe and effective in children under 10 years of age.
WHAT DRUGS INTERACT WITH LAMICTAL?
Lamictal may interact with carbamazepine, phenytoin, phenobarbital, primidone, or rifampin.
Lamictal may also interact with hormonal forms of birth control (pills, injections, implants, or skin patches), divalproex, oxcarbazepine, or valproic acid.
WHAT DRUGS INTERACT WITH SEROQUEL?
Seroquel may interact with seizure medications.
Seroquel may also interact with other medicines that make you sleepy (cold or allergy medicine, sedatives, narcotics, sleeping pills, muscle relaxers, and medicine for seizures, depression, or anxiety), medications to treat high blood pressure or a heart condition, medications to treat Parkinson’s disease, steroids, antibiotics, antifungals, anti-malaria medications, heart rhythm medicines, medications to treat HIV or AIDS, migraine headache medicines, or other antidepressant or medicines to treat psychiatric disorders.
can you take seroquel with lamictal
While periods of mania are a major characteristic of bipolar disorder, evidence suggests it is the depressive symptoms that contribute to most of the long-term disability associated with this condition. However, the use of antidepressants in bipolar therapy—especially for long-term maintenance—remains controversial.
Some studies suggest that antidepressants may lead to relapse of mania. While others suggest the medications may increase the risk of future depressive episodes.
Jay Amsterdam
In contrast, Jay Amsterdam, M.D., head of the Depression Research Unit at the University of Pennsylvania Perelman School of Medicine. And colleagues found evidence to suggest that the serotonin-norepinephrine reuptake inhibitor venlafaxine was at least as effective as lithium as a maintenance therapy in regards to risks of new depressive or manic symptoms.
Antipsychotics such as quetiapine may be another option for patients. While they are effective for acute bipolar depression, there is not much evidence for their long-term efficacy. Likewise, lamotrigine approved to help prevent relapse of bipolar depression. But there is uncertainty about how well it works in the acute phase of bipolar depression, given that it requires a slow titration period to reach an optimal dose.
Lancet Psychiatry
A study published in Lancet Psychiatry now suggests that combining these two agents might offer sustained benefits for patients.
In a randomized trial, 202 participants with bipolar depression with a recent acute depressive episode received lamotrigine. Or placebo as well as 500 microgram of folic acid or placebo daily in addition to quetiapine.
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