Adult Bipolar Disorder Research Articles

Altered neurochemistry in the anterior white matter of bipolar children and adolescents: a multivoxel 1H MRS study.

Abnormalities within frontal lobe grey and white matter of bipolar disorder (BD) patients have been consistently reported in adult and pediatric studies, yet little is known about the neurochemistry of the anterior white matter (AWM) in pediatric BD and how medication status may affect it. The present cross-sectional 3T 1H MRS study is the first to use a multivoxel approach to study the AWM of BD youth. Absolute metabolite levels from four bilateral AWM voxels were collected from 49 subjects between the ages of eight and eighteen (25 healthy controls (HC); 24 BD) and quantified. Our study found BD subjects to have lower levels of N-acetylaspartate (NAA) and glycerophosphocholine plus phosphocholine (GPC+PC), metabolites that are markers of neuronal viability and phospholipid metabolism and have also been implicated in adult BD. Further analysis indicated that the observed patterns were mostly driven by BD subjects who were medicated at the time of scanning and had an ADHD diagnosis. Although limited by possible confounding effects of mood state, medication, and other mood comorbidities, these findings serve as evidence of altered neurochemistry in BD youth that is sensitive to medication status and ADHD comorbidity.

Emotional regulation neural circuitry abnormalities in adult bipolar disorder: dissociating effects of long-term depression history from relationships with present symptoms

Bipolar disorder (BD) is common and debilitating and confounding effects of depression history on neural activity in BD are unknown. We aimed to dissociate neural activity reflecting past depression-load vs. present symptom severity using the Course and Outcome of Bipolar Youth (COBY), a prospective longitudinal cohort study of pediatric-onset BD. In n = 54 COBY (18–32 years), we modeled depression scores over time (up to 17.5 years) using a standardized autoregressive moving average (ARMA) model, followed by k-means cluster analysis. N = 36 healthy participants (HC, 20–36 years) were included. Using two factorial analyses, we parsed the impact of ARMA-defined past depression-load on neural activity from the impact of current symptoms on neural activity (p < 0.001, k > 30) and examined relationships with past and present symptoms (ps FDR-corrected). ARMA identified three COBY groups based on past depression-load. ARMA-defined COBY participants with the greatest past depression-load vs. other groups showed greater activity in right temporoparietal junction, thalamus, insula, premotor cortex, left fusiform gyrus, bilateral precuneus and cerebellum. In contrast, BD-COBY participants vs. HC showed greater activity in left hippocampus, dorsolateral prefrontal cortex, and right somatosensory cortex, plus the above thalamus, premotor cortex and cerebellum; activity positively correlated with present symptom severity in most regions. Past depression-load was related to social cognition and salience perception network activity, potentially reflecting heightened attention to socially relevant distracters, while present symptoms were associated with emotion processing and reappraisal network activity, potentially reflecting abnormal emotional experience and regulation. Differentiating aberrant neural activity related to long-term depression vs. present affective symptoms can help target interventions to networks associated with pathophysiological processes, rather than long-term illness effects.

P.748 Quetiapine's role as a maintenance treatment in bipolar disorder in adults

P.748 Quetiapine's role as a maintenance treatment in bipolar disorder in adults

474 - Special considerations for lithium use in Older Age Bipolar Disorder

Lithium is the oldest and still one of the most frequently prescribed mood stabilizers in the treatment of bipolar disorder. Though, the implications of lithium use in the older population remain less understood. This work aims to provide an understanding of the impact of lithium in older age bipolar disorder, including tolerability and efficacy.A non-systematic review was performed on PubMed database, using the key words “lithium older adult bipolar disorder” and references from recent international bipolar disorder guidelines.There is an evidence base that lithium is effective in older age bipolar disorder. Aging-associated pharmacokinetic and pharmacodynamic changes as well as increased rates of medical comorbidities and polypharmacy predispose older patients to a higher risk of lithium toxicity. Careful monitoring and adjustment of lithium dosage is especially important in older adults to minimize the risk of toxicity.

The influence of social, psychological, and cognitive factors on the clinical course in older patients with bipolar disorder.

Research on factors that contribute to recurrence in older adults with bipolar disorder (OABD) is sparse. Previous research showed that clinical factors (e.g., age of onset, lifetime psychotic features, and suicide risk) were not associated with the recurrence in OABD. In younger adults, worse social functioning, coping style, and worse cognitive functioning are found to be associated with an unfavorable course of bipolar disorder. Therefore, this study is focusing on social, psychological, and cognitive factors in OABD. More insight in these factors is essential in order to develop and further specify preventive and treatment interventions. Data were used from the Dutch Older Bipolars (DOBi) cohort study. We included 64 patients for 3-year follow-up measurements, who were divided in a recurrent group and a nonrecurrent group. Logistic regression analyses were conducted to assess associations between social, psychological, and cognitive factors, and nonrecurrence. 39.1% reported at least one recurrence during the 3-year follow-up period. No significant associations were found between the social, psychological, and cognitive factors and having a recurrence during the follow-up period. Participants in the recurrent group were younger, more often female and less likely to have children. Our results suggest that results from the adult bipolar disorder population cannot be extrapolated to OABD patients, underlining the need for longitudinal studies in OABD.

A Comprehensive Review of the Evaluation, Diagnosis, and Treatment of Older Adult Bipolar Disorder

This review summarizes the extant literature on the epidemiology, neuropsychology, clinical assessment, and treatment/management of older adult bipolar disorder (OABD). The primary aim was to provide a contemporary and accessible reference for clinicians involved in the care of OABD patients. Important research into the unique features of OABD has been carried out in recent years, providing a more robust albeit still limited foundation to help guide clinical decision-making. Some of the more consistent findings have highlighted (1) the importance of assessing for potentially reversible sources of secondary mania (i.e., manic symptoms unrelated to a primary mood disorder but with qualitatively similar presentation) in patients with late-onset mania; (2) the need for closer follow-up and more aggressive treatment to help stabilize illness course in OABD patients with earlier symptom onset; (3) the presence of domain-general cognitive dysfunction (but not accelerated cognitive aging) in OABD; and (4) the strong need for more randomized control trials examining the safety and efficacy of various psychopharmacological interventions in OABD samples. Research continues to support lithium as the gold-standard treatment for OABD, but there are other promising therapies. Asenapine, lurasidone, and divalproex have demonstrated efficacy in reducing symptoms, but future research must also categorize their side effect profile and most effective use in treatment (e.g., monotherapy or adjunctive therapy). ECT may be a useful alternative to pharmacotherapy, but very little research has been conducted in the OABD patient population. Compared with mixed age and younger samples, there is a paucity of clinical research specific to OABD. To date, the treatment literature in OABD is limited by small sample sizes, cohorts of mixed-age populations, and non-randomized and uncontrolled study designs. Consequently, making evidence-based treatment decisions often requires extrapolating data from studies of younger adults with BD. Fortunately, international collaborative efforts have recently been established that will include, for the first time, much larger sample sizes to better characterize the natural history, clinical course, comorbidities, and effective therapies for OABD.

Brain-derived neurotrophic factor in bipolar disorder: Associations with age at onset and illness duration

Bipolar disorder (BD) is a heterogeneous disorder that contains neurodevelopmental differences. Defining homogeneous subgroups of BD patients by using age at onset (AAO) as a specifier may promote the classification of biomarkers. This study compares peripheral BDNF levels between pediatric and adult BD patients to investigate the associations between BDNF levels, AAO, and illness duration. We enrolled two groups of euthymic patients, those with pediatric BD (n = 39) and those with adult BD (n = 31), as well as a group of healthy controls (HCs) (n = 90). Participants were assessed using clinical measures and BDNF serum levels were obtained using ELISA. We observed that BDNF levels were comparable between adult BD and HCs, but were clearly lower in pediatric BD than in HCs. In adult BD with AAO ≥30 years, BDNF levels were significantly higher than in adult BD with AAO <30 years. In pediatric BD, patients with prepubertal-onset had higher BDNF levels than those with pubertal-onset. BDNF levels demonstrated the accuracy of being able to distinguish pediatric BD from healthy controls in a receiver operating characteristic (ROC) curve analysis (area under the curve [AUC] = 0.792). In adult BD, higher BDNF levels were associated with later disease onset, but this was not the case in pediatric BD. Finally, reduced BDNF levels were associated with illness duration in adult BD. The findings indicate that BDNF levels in BD patients are associated with AAO. BDNF may, therefore, potentially serve as a developmental marker in BD, when AAO is taken into account.

Correlation Between Decreased Amygdala Subnuclei Volumes and Impaired Cognitive Functions in Pediatric Bipolar Disorder.

BackgroundThe amygdala has been proposed to be involved in the pathophysiology of pediatric and adult bipolar disorder (BD). The goal of this structural magnetic resonance imaging (sMRI) study was to investigate the morphometric characteristics of amygdala subnuclei in patients with pediatric bipolar disorder (PBD) compared to healthy controls (HCs). Simultaneously, we examined correlation between amygdala subnuclei volumes and cognitive dysfunction.Materials and MethodsWe assessed 40 adolescent outpatients, diagnosed with manic or euthymic PBD according to the DSM-5 criteria for BD and 19 HCs. Cognitive functions were evaluated using a Stroop color-word test (SCWT), trail making test (TMT), visual reproduction immediate recall subtest (VR I), and digit span subtest (DST). Amygdala and its subnuclei structures were automated segmented using FreeSurfer software and the volumes of them were compared between groups and correlation with clinical and cognitive outcomes was conducted.ResultsManic patients exhibited significantly decreased volumes in the bilateral whole amygdala and its basal nucleus, cortico-amygdaloid transition (CAT), and accessory basal nucleus (ABN) compared with HCs. Euthymic patients had decreased volume in the bilateral ABN and left CAT. In addition, we found significant positive associations between VR I scores and the right whole amygdala and its bilateral basal, right lateral, and ABN volumes in the manic group.ConclusionThese findings support previous reports of smaller amygdala volumes and cognitive dysfunctions in PBD, and further mapping abnormalities to specific amygdala subnuclei. Correlation between basolateral volume and VR I of PBD may expand our understanding of neural abnormalities that could be targeted by treatment.

Allostatic load, emotional hyper-reactivity, and functioning in individuals with bipolar disorder.

Diagnosis and management of bipolar disorder (BD) are limited by the absence of available biomarkers. Allostatic load (AL) represents the strain that stress, including the effects of acute phases and inter-episode chronic mood instability, exerts on interconnected biological systems. This study aimed to operationalize an AL index and explore whether it could be relevant to better characterize BD patients with and without emotional hyper-reactivity particularly those at higher risk of immune-cardiometabolic dysregulation and functional impairment. Levels of biomarkers of chronic inflammation (hsCRP and albumin), cardiovascular (systolic/diastolic blood pressure) and metabolic functions (fasting glucose, glycosylated hemoglobin, total cholesterol, LDL, HDL, and triglycerides) were measured in 1072 adult BD outpatients. Patients were classified in two groups (with/without emotional hyper-reactivity) assessed by the Multidimensional Assessment of Thymic States scale. An Allostatic Load Index for BD (BALLI), comprising six biomarkers, was constructed using data-driven biomarker selection. BALLI showed 81.1% accuracy with good sensitivity (81%) and specificity (81.2%) for characterizing BD patients presenting emotional hyper-reactivity, elevated risk of inflammation (increased hsCRP, hypoalbuminemia) and cardiometabolic disturbances (hypertension, hyperglycemia, and hypertriglyceridemia). Patients classified by the BALLI as presenting emotional hyper-reactivity had significantly lower global and cognitive functioning than those without emotional hyper-reactivity (P<.0001). A multidimensional approach based on a simple AL score (eg, BALLI) and dimensions of behavior (eg, emotional hyper-reactivity) alongside mood is clinically relevant. AL index could be a useful tool to detect multisystemic physiological dysregulations in BD patients with/without emotional hyper-reactivity particularly those at higher risk of immune-cardiometabolic disturbances and functional impairment.

Brain perfusion during manic episode and at 6-month follow-up period in bipolar disorder patients: Correlation with cognitive functions.

BackgroundPatterns of altered cerebral perfusion and cognitive dysfunction have been described in Bipolar Disorder (BD) acute episodes and euthymia. Knowledge of the relationship between cognitive function and perfusion in a manic state and status when followed up is still limited.ObjectiveTo describe brain perfusion alterations and its relationship with cognitive impairment in patients with BD during manic episodes and after 6 months.MethodsObservational‐prospective study in 10 type I BD adults during moderate‐severe manic episodes. We assessed sociodemographic data and clinical variables as well as cognitive function through Screening for Cognitive Impairment in Psychiatry (SCIP‐S). Finally, we performed a Brain Perfusion SPECT using a Tc99m‐ethyl cysteine dimer.ResultsDuring manic episodes, patients showed cognitive impairment with a mean SCIP‐S score of 63.8 ± 17.16. This was positively correlated with perfusion measured as relative reuptake index (RRI) at the right temporal pole (ρ = 0.65 p = .0435) and negatively correlated with right the orbitofrontal cortex (ρ = −0.70 p = .0077) and the right subgenual cingulate cortex (ρ = −0.70 p = .0256). Episode severity measured by the Young Mania Rating Scale (YMRS) positively correlated with RRI at the right temporal pole (ρ = 0.75, p = .01). At follow‐up, six patients were taking treatment and were euthymic, we found a negative correlation with the YMRS and RRI at the bilateral orbitofrontal cortex (ρ = −0.8827, p = .019). They did not show significant improvement in cognitive performance at SCIP‐S, and there was negative correlation with the following of the SCIP‐S subscales; processing speed with the bilateral dorsolateral prefrontal, the bilateral medial prefrontal, the left temporal pole cortex RRI, and verbal fluency with the bilateral anterior cingulate cortex RRI.ConclusionCognitive impairment was correlated with brain perfusion patterns at baseline and follow‐up. Large sample size studies with longer follow‐up are needed to describe the changes in perfusion and cognitive functions in BD.

Rate of diagnostic conversion to bipolar disorder in adults with unipolar depression and psychopharmacological treatment in the republic of Korea: A nationwide register-based study

BackgroundPatients with bipolar disorder (BD) and depressive episodes are usually diagnosed with major depressive disorder (MDD). It is clinically important to estimate diagnostic conversion rate from MDD to BD and identify factors characterizing MDD patients at highest risk. We investigated conversion rate from depression to BD, stratified by age and sex, and associated psychopharmacological treatment patterns. MethodsData were extracted from the National Health Insurance to include 817,759 patients 18 years or older with new-onset antidepressant-treated depression between 2011 and 2015. We estimated rate of conversion from unipolar depression to BD stratified by age and sex during follow-up (357,343 person-years) and investigated the related medication patterns. ResultsDuring follow-up (median, 155 days; range, 2–1,442 days), 19,179 patients had diagnostic conversion to BD. Conversion rate was highest for patients aged 18–29 years; it gradually decreased with age until 60–69 years. Overall conversion rate to BD was 58.48 per 1,000 person-years for males and 50.97 per 1,000 person-years for females. For patients aged 18–39 years, the rate was higher for females. Patients with conversion to BD were prescribed more antidepressants. When the diagnosis changed to BD, 51% of patients were prescribed additional antipsychotics and/or mood stabilizers. LimitationsThe limited follow-up period may have underestimated conversion rate to BD. Data were restricted to participants with pharmaceutically treated depression. ConclusionsThe rate of diagnostic conversion from depression to BD differed by sex and age and was highest for females aged 18–29 years. Diagnostic conversion was accompanied by relevant prescription changes.

Anxiety disorders comorbidity in pediatric bipolar disorder: a meta‐analysis and meta‐regression study

Anxiety disorders (AD) are known for its comorbidity and negative impact on the course of adult bipolar disorder (BD). However, there is limited research on AD comorbidity in pediatric BD (PBD). Here, we aimed to conduct a meta-analysis and meta-regression study about the comorbidity and covariates of AD and PBD. We systematically searched relevant articles published until May 2019, as defined in PRISMA guidelines. Variables for associated features and prevalence of AD were extracted. Thirty-seven articles represented data for the analysis. Lifetime any AD comorbidity was 44.7%; panic disorder (PD) was 12.7%; generalized anxiety disorder (GAD) was 27.4%; social phobia was 20.1%; separation anxiety disorder (SAD) was 26.1%; and obsessive-compulsive disorder (OCD) was 16.7%. Childhood-onset studies reported higher GAD and SAD comorbidity, while adolescent-onset studies reported higher PD, OCD, and social phobia. Age of onset, gender, comorbidity of ADHD, substance use, oppositional defiant disorder and conduct disorder affected each anxiety disorders' comorbidity with PBD differently. Anxiety disorders are highly comorbid with PBD. Early-onset PBD increases the risk of AD. Biopsychosocial aspects of this comorbidity and its course needs to be evaluated further.

Fully Automated Habenula Segmentation Provides Robust and Reliable Volume Estimation Across Large Magnetic Resonance Imaging Datasets, Suggesting Intriguing Developmental Trajectories in Psychiatric Disease

Studies of habenula (Hb) function and structure provided evidence of its involvement in psychiatric disorders, including schizophrenia and bipolar disorder. Previous studies using magnetic resonance imaging (manual/semiautomated segmentation) have reported conflicting results. Aiming to improve Hb segmentation reliability and the study of large datasets, we describe a fully automated protocol that was validated against manual segmentations and applied to 3 datasets (childhood/adolescence and adult bipolar disorder and schizophrenia). It achieved reliable Hb segmentation, providing robust volume estimations across a large age range and varying image acquisition parameters. Applying it to clinically relevant datasets, we found smaller Hb volumes in the adult bipolar disorder dataset and larger volumes in the adult schizophrenia dataset compared with healthy control subjects. There are indications that Hb volume in both groups shows deviating developmental trajectories early in life. This technique sets a precedent for future studies, as it allows for fast and reliable Hb segmentation and will be publicly available.

The frequency of childhood abuse in bipolar disorder and its impact on the clinical course

Aim: There is a growing awareness of the association between physical and sexual abuse and subsequent development of psychopathology, but little is known about the prevalence and long-term effects of childhood abuse in bipolar disorder. The aim of this study was to investigate the relationship between childhood abuse and adult bipolar disorder. Material and Methods: 50 female and 42 male bipolar I or II disorder out-patients who were in remission were evaluated. Demographic data, comorbid Axis 1 disorder, history of childhood abuse, family history, suicide attempts and social factors that are associated with the course of illness were investigated.Results: Childhood abuse was reported in 54.3% of the bipolar patients in this study. The incidence of abuse was higher in women. While women were exposed to more sexual abuse, physical abuse was more common in men. The most common type of abuse was neglect. There was no significant difference in sociodemographic variables and family characteristics between patients with history of abuse and patients without history of abuse. Patients who endorsed a history of physical and sexual abuse and neglect compared with those who did not, had an earlier onset of bipolar illness, a higher rate of combined pharmacotherapy and increased number of comorbid disorders, especially post-traumatic stress disorder(PTSD).Conclusion: Greater appreciation of the relationship between early traumatic experiences and an adverse course in bipolar disorder should lead to preventive and early intervention measures that may reduce the associated risk of a poor outcome.

19.2 THE COLLABORATIVE LITHIUM TRIALS

Lithium has been known to be a safe and effective treatment for bipolar disorder in adults. However, there was little research regarding the use of lithium in youth with bipolar disorder. The Collaborative Lithium Trials (CoLT) is a series of multisite studies examining the safety and efficacy of lithium for the treatment of bipolar disorder in youth.

Lower estimated intelligence quotient is associated with suicide attempts in pediatric bipolar disorder

BackgroundApproximately 20% of individual with pediatric bipolar disorder (PBD) have a lifetime history of suicide attempt. Some cognitive measures were associated with a suicide attempt, but no study has assessed the association of this event with the estimated intelligence quotient (IQ) in PBI. In adult Bipolar Disorder no association between IQ and suicidality was found, with different correlations between cognitive measures. There are studies in general population showing a negative correlation and others did not find any association. In Schizophrenia, IQ had a positive correlation with suicide attempt. So, the correlation between IQ and suicidality still controversial. MethodsWe recruited 63 children and adolescents younger than 18 years of age with PBD based on DSM-IV criteria from an outpatient clinic in Brazil. Manic and depressive symptoms were assessed with the YMRS and CDRS, respectively. Estimated IQ was assessed with the WISC-III. The presence or absense of suicidal attempt, clinical and demographic variables were assessed with the K-SADS-PL-W. ResultsPatients who attempted suicide had lower estimated IQ compared to patients who did not attempt suicide (82.72 ± 18.70 vs. 101.0 ± 14.36; p = 0.009). This finding remained after correction for depressive symptoms and family income (OR = 0.94; 95% CI = 0.89 - 0.99; p = 0.029). LimitationsSmall sample, reverse causality could not be discarded, we only used two subscales of the WISC-III to estimate intelligence. ConclusionEstimated IQ and suicide attempts were negative correlated in PBD. Future longitudinal and larger studies may confirm our findings.

More Evidence for Lithium’s Benefits in Youth Emerges

More Evidence for Lithium’s Benefits in Youth Emerges

Complex polypharmacy in bipolar disorder: Side effect burden, adherence, and response predictors

BackgroundComplex polypharmacy (CP) is common in bipolar disorder (BD). We assessed the associations between CP, adherence, and side effect burden, and patient traits associated with clinical improvement in relationship to CP. MethodsWe conducted a secondary analysis of 482 adult BD participants in the Bipolar CHOICE trial. We examined the associations between CP (use of ≥3 BD medications) and non-adherence (missing >30% of BD medication doses in the last 30 days) and side effect burden (Frequency, Intensity and Burden of Side Effects Rating scale) using multivariate models with patient random effects. We used logistic regression to assess the patient traits associated with remission among those with majority CP use (Clinical Global Impression-Severity for BD score ≤2 for 8+ weeks). Results43% of patients had any CP and 25% had CP for the majority of the study. CP was associated with non-adherence (OR = 2.51, 95% CI [1.81, 3.50]), but not worse side effect burden. Among those with CP, 16% achieved remission; those with non-adherence, comorbid social or generalized anxiety disorder, or BD I vs. II were less likely to achieve remission among those with CP. LimitationsThere could be unmeasured confounding between use of CP and side effect burden or adherence. Adherence was measured by self-report, which could be subject to reporting error. ConclusionsBD patients with CP were less likely to adhere to therapy, and those with worse adherence to CP were less likely to clinically respond. Clinicians should assess medication adherence prior to adding another agent to medication regimens.

Neuropsychological profiles of adult bipolar disorder patients with and without comorbid attention-deficit hyperactivity disorder

BackgroundComorbid attention-deficit/hyperactivity disorder (ADHD) is common in bipolar disorder and associated with worse outcomes. Cognitive testing might be a tool to identify this group. Here we compare the neuropsychological profiles of bipolar disorder patients with (BD + cADHD) and without (BD − cADHD) childhood attention-deficit hyperactivity disorder.MethodsAdult patients with BD − cADHD (n = 66), BD + cADHD (n = 32), and healthy controls (n = 112) were tested using a comprehensive battery of neuropsychological tests. Patients underwent rigorous diagnostic assessments for bipolar disorder and ADHD, as well as a parental interview to establish childhood ADHD.ResultsThe neuropsychological profiles of the groups were similar, except that the BD + cADHD group performed significantly worse on working memory. Working memory did not differ between those in the BD + cADHD group who only had a history of childhood ADHD and those that still met criteria for ADHD in adulthood.ConclusionsCognitive testing had limited power to differentiate between bipolar disorder adults with and without childhood ADHD. The BD + cADHD subgroup cannot explain the significant cognitive heterogeneity seen in bipolar disorder patients.

Effect of permeation enhancers on in vitro release and transdermal delivery of lamotrigine from Eudragit\xaeRS100 polymer matrix-type drug in adhesive patches

The drug-in-adhesive (DIA)-type matrix patches of lamotrigine are developed using variable permeation enhancers (oleic acid, PG, lemon oil and aloe vera), and drug in vitro release and its permeation are evaluated. Lamotrigine has been long used as an anti-epileptic, mood stabilizer, to treat bipolar disorder in adults and off label as an antidepressant. lamotrigine matrix patches comprising of Eudragit®RS100 (rate-controlling polymer) and DuroTak® 387-2510 (adhesive) were prepared by pouring the solution on backing membrane (3M-9720). The thickness of 120 µm was adjusted through micrometer film applicator. USP Apparatus V was used for the evaluation of release profile, which was fitted into various mathematical models. Quality characteristics of patches were determined through weight variation, moisture content, moisture uptake and drug content evaluation. FTIR studies were performed for drug-excipient compatibility; Franz diffusion cell was employed for studying in vitro permeation parameters such as flux, lag time, and ER. Skin sensitivity study of optimized patch was also performed. The release from patches comprising of PG and oleic acid was maximum, i.e., 96.24 ± 1.15% and 91.12 ± 1.11%, respectively. Formulations (A1–A5) exhibited Makoid–Banakar release profile. Formulation A3 consisting of oleic acid was optimized due to enhanced permeation of drug across skin compared to other enhancers with enhancement ratio of 3.55. Skin sensitivity study revealed patch as safe and non-allergenic. The study demonstrates that oleic acid can be used as a suitable permeation enhancer for transdermal delivery of lamotrigine from matrix-type patches.