Lamotrigine monotherapy for management of bipolar depression with comorbid obsessive-compulsive disorder in a second trimester anemic pregnant female

Abstract

This text discusses a case report of a pregnant anemic female in her second trimester with a diagnosis of bipolar depression and comorbid obsessive compulsive disorder (OCD). Managing both mood stabilization and obsessive compulsive symptoms simultaneously in a pregnant female presents a real challenge, especially considering that serotonin reuptake inhibitors (SSRI), the first-line treatment for OCD, can induce manic or mixed mood states in bipolar disorder patients. This case is unique in view of limited options left with pregnancy in place. Lamotrigine was chosen as an agent and was introduced in this patient which is rated as FDA pregnancy risk category C which amounts to risk cannot be ruled out (human data lacking, animal studies positive or not done). Patient responded well and maintained well on monotherapy of lamotrigine and showed significant improvement in both symptoms of depression and OCD. USG-level II examination shows no abnormality on repeated scans.

One of the most prevalent co-occurring conditions with bipolar disorder (BD) is obsessive-compulsive disorder (OCD).[1] When co-morbid OCD and BD (OCD-BD) presents, clinicians are frequently faced with difficulty in choosing appropiate treatment options. This is because medication for OCD can trigger or exacerbate mood instability, and psychotherapy techniques for OCD may not be practical in cases of acute mania and depression.[2] Population studies show that the lifetime prevalence of BD comorbidity in OCD subjects varies with a huge range of findings (0.3–53.3%).[1] However, a recent meta-analysis conducted in 2020 suggests that the cross-sectional prevalence of OCD in BD patients is 11.2% and the lifetime prevalence rate was 10.9% suggesting that in BD patients OCD symptomatology is chronic rather than episodic.[3] Compared to the lifetime OCD prevalence of 2.5% in the general population, the lifetime prevalence of comorbid OCD in BD patients was about 4.4 times higher.[3] Another recent meta-analysis reported a higher prevalence of OCD during pregnancy (2.07%) and the postpartum period (2.43%) compared to the general population (1.08%).[4] Lamotrigine, a mood stabilizer can be used as monotherapy in maintenance phase for Bipolar Disorder-II (BD-II) as per Canadian Network for Mood and Anxiety Treatments (CANMAT), 2018 guidelines but for OCD, it is an augmenting agent to a primary selective serotonin reuptake inhibitor (SSRIs) or serotonin and nor-epinephrine reuptake inhibitors (SNRIs) agent as per Indian Psychiatric Society (IPS) guidelines for management of OCD.[5,6]

A 35-year-old married woman, currently in her 4^th pregnancy, whose academic history indicated that the patient had no formal education, presented to the obstetric emergency department because of poor oral intake and inability to take care of herself. Consultation Liaison Psychiatry team was informed given complaints of poor self-care and oral intake. Upon evaluation, the patient has a 6-year-long psychiatric illness, initially characterized by obsessive-compulsive symptoms comprising obsessive rituals, obsessive doubts, obsessive dirt and contamination and associated compulsive checking, need for symmetry, and compulsive washing. Initially, she did not receive treatment, but after she was started on fluoxetine (40 mg) for her OC (obsessive compulsive) symptoms, she had a Treatment Emergent Affective Switch (TEAS) ie. a manic switch. Following this she was admitted to a hospital where she was started on sodium valproate (750–1000 mg). There was gradual resolution of her manic symptoms. Her OC symptoms were exacerbated as manic symptoms resolved. She had two episodes of mania with psychotic symptoms (2021, 2023), each lasting 2 months, and was never on maintenance treatment. Each time there was a reduction of OC symptoms during an episode but further exacerbation of OC symptoms occurs upon remission [Figure 1].

Figure 1.

Life chart of described patient. (Severity of mood symptoms mentioned on Y-axis; Blue box: manic episode; Green box: Depressive episode; Red line: Obsessive compulsive symptoms)

At the time of presentation, she was pregnant (period of gestation: 4 months) with anemia (Hb: 7 gm%). She was having persistent and pervasive low mood, crying spells, anhedonia, poor self-care, reduced appetite, somatic symptoms, decreased psychomotor activity, and passive death wishes which started 2 months ago. She also has a similar set of OC symptoms as mentioned previously. She was diagnosed according to ICD-11 as Bipolar type 1 disorder, current episode depressive, severe without psychotic symptoms (6A60.6), and obsessive and compulsive disorder with poor to absent insight (6B20.1). Her score on the Hamilton Depression Rating Scale (HAM-D) at the time of admission was 41 (i.e. severe depression), and on Yale-Brown Obsessive–Compulsive Scale (YBOCS) was 35 (i.e. extreme OCD).

She received 3 units of packed red blood cells (PRBCs) owing to her severe anemia. Treatment options were explored but got complicated with patients being pregnant. SSRI was ruled out because of the history of a manic switch. She was started on CBT for OCD but due to her educational status, she could not follow the instructions. Family members denied modified electroconvulsive therapy despite proper psychoeducation. She was planned to start on oral lamotrigine and was started on 25 mg which was gradually increased to 50 mg over 3 weeks. The patient started improving and there was gradual improvement in symptoms and there was a reduction in the score of both scales. At the time of discharge after a ward stay of 18 days, her scores on HAM-D were 7 and YBOCS was 10. The patient maintained well and followed up in OPD after 1 week of discharge. She continued to follow up every month henceforth and has been maintaining well on 100 mg of lamotrigine. The fetal scan showed no anomaly and the patient has been following up with the department of obstetrics.

According to CANMAT 2018 guidelines, first-line pharmacological agents in BD depression are lithium, lamotrigine (monotherapy and adjuvant), quetiapine, and lurasidone with combinations of either lithium or divalproex sodium and lurasidone. Second-line options include divalproex sodium, SSRI with adjuvant bupropion, olanzapine and fluoxetine combination, modified electroconvulsive therapy (ECT), and cariprazine.[5] As the patient was pregnant, special considerations were made for treatment and some options were ruled out based on it. The use of sodium valproate was not considered due to risk of teratogenicity, SSRIs were avoided due to a history of TEAS, mECT was not considered as family members denied consenting for mECT despite multiple attempts to explain the need and safety of mECT in pregnancy, and quetiapine monotherapy was not considered as no report of quetiapine monotherapy in co-morbid OCD-BD[5,7] has been reported.

Lamotrigine is one agent that has been implicated in both bipolar depression and as an adjuvant therapy for OCD.[5,6] Lamotrigine is a Category C drug in pregnancy.[8] Drugs belonging to Category C means that animal reproduction studies have shown an adverse effect on the fetus, there are no adequate and well-controlled studies in humans, and the benefits from the use of the drug in pregnant women may be acceptable despite its potential risks, or animal studies have not been conducted and there are no adequate and well-controlled studies in humans.[9] A recent cohort study conducted in 2024 involving pregnant females showed that offspring exposed to lamotrigine had the lowest prevalence of Major Congenital Malformation when compared with other anti-seizure medications.[10]

The case report highlights the potential of lamotrigine as a monotherapy for comorbid OCD and BD, controlling both symptoms without affecting pregnancy. However, further studies are needed to determine its effectiveness and provide evidence to support it. The aforementioned case was probably the first reported case in which lamotrigine monotherapy was used to treat such a delicate situation, where treatment options are limited and thus management becomes challenging.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient has given her consent for her images and other clinical information to be reported in the journal. The patient understands that her name and initials will not be published and due efforts will be made to conceal identity, but anonymity cannot be guaranteed.

Data availability statement

All information mentioned here is of a patient and is avilaible with hospital medical record section.

Authors' contributions

AS, MRT and SP were involved in care and management of patient. MRT and AS completed the literature review and manuscript preparation. SP reviewed the manuscript prior to submission. All authors contributed substantially to the write-up of the article and all take responsibility of the content of the publication.

Conflicts of interest

There are no conflicts of interest.

Funding Statement

Nil.