The patient is a 34-year-old, single, unemployed, Hispanic female with a previous history of Bipolar I disorder diagnosed for 8 years, as well as issues with long-term cocaine and alcohol dependence. She began a residential drug rehabilitation program 2 weeks before presenting for her intake interview at our outpatient clinic. She presented to the clinic with complaints of having depressed mood and decreased energy levels of 1-week duration. The patient also reported having crying spells, decreased sleep with early morning insomnia, and decreased appetite without recent weight loss. She reported no psychotic or manic symptoms. No substance abuse was reported at the time of presentation since the start of her rehabilitation program. Her past history included reported major depressive episodes and manic episodes during a period of abstinence from drugs, suicidal ideation and two suicide attempts in the past.
Family history of psychiatric illness included her mother having a bipolar disorder diagnosis; her brother having a diagnosis of major depression; with both parents having a history of alcohol and cocaine abuse. Her birth and developmental history was unremarkable, with normal developmental milestones reached during childhood.
Her medical history included seizure disorder, systemic lupus erythematosus and hypothyroidism. Her current medication regimen included citalopram 20 mg/day; carbamazepine 300 mg/day; and thyroxine 100 mcg/day.
On examination, patient was 5-foot, 1-inch tall and weighed 170 lb. She appeared to be her stated age and was well nourished with appropriate clothing. She was awake, alert and oriented to time, place and person. Her posture was appropriate and motor activities were normal. Her speech was soft with normal stream. The patient was cooperative with good eye contact. She was open and engaging with the interviewer. Her mood was depressed and her affect was appropriate to thought content, full range. Her thought form was coherent. No suicidal or homicidal ideation was elicited at that time. She reported no delusions, hallucinations, obsessions or phobias. Her memory and cognitive function were grossly intact. Her insight into her illness was intact and showed good judgment and impulse control.
Laboratory data included: complete blood count, complete metabolic panel, urine analysis, thyroid function tests and liver function tests and were within normal range. Urine toxicology report was negative. First-line bipolar I disorder treatment choices of lithium and depakote, as well as second-line treatment choices, such as lamotrigine, were discussed with the patient in detail. The patient agreed to treatment and was initiated on lamotrigine 50 mg/day for weeks 1 and 2, with a plan in place to increase to 50 mg twice a day and titrate up to usual maintenance dose of 200 mg orally daily. Carbamazepine and thyroxine were continued at previous dosage; however, citalopram was discontinued. The patient was instructed to continue with her residential rehabilitation program and to follow up with her psychiatrist after 2 weeks.
During her first follow-up visit, the patient reported an increasingly depressed mood, and intermittent episodes of suicidal ideation without plan in the 3 days before her visit, which were increasing in intensity after increase of lamotrigine. The decision to stop lamotrigine was made due to the increased intensity of suicidal thoughts that seemed to correlate with the increase in dosage. The patient was started on valproate 750 mg in the morning and 1,000 mg at nighttime as per patient’s weight.
Since the patient was residing in a supervised setting and did not have active suicidal ideation at time of evaluation, she was able to return to her residential rehabilitation program. The physician with program staff arranged close supervision of suicidality and a follow-up visit in 1 week was scheduled.
During her next follow-up visit, she reported no suicidal ideation, and significant improvement in her mood, sleep, and appetite were also noted. However, the patient still had mild depressive symptoms. Valproate was increased to 1,000 mg twice a day, as previous VPA level was 54 mg/dL. Follow-up VPA level was: 79 mg/dL and the patient’s mood symptoms were well controlled. No side effects were reported. The patient was scheduled for regular follow-up.
On next follow-up visit, the patient’s depressive symptoms had resolved. No suicidal ideations were reported. Mood was stable. Valproate levels remained within therapeutic range. The patient was satisfied with treatment effectiveness and motivated to continue treatment as scheduled.
Lamotrigine-Induced Suicidal Ideation
Bipolar disorder (BD) is a highly recurrent, lifelong mood disorder characterized by episodes of mania and depression in the same patient at different times.1 It takes an average of 8 to 10 years before the correct diagnosis can be established, sometimes longer in BD II patients.1
Currently, there is a variety of medication available for the treatment of BD. Interestingly, none of them were specifically developed for BD.2 The goal of treatment in BD is long-term stability, regaining and maintaining full functionality and a good quality of life.2 Agents approved by the US Food and Drug Administration (FDA) to treat bipolar depression and bipolar mood episodes are an olanzapine-fluoxetine combination, quetiapine monotherapy for acute treatment, and lamotrigine for maintenance and preventive treatment.3
Lamotrigine was first introduced into clinical practice as an antiepileptic drug in Europe in 1990, and its safety and tolerability profiles in epilepsy are well characterized based on its clinical use and extensive study in clinical trials.4 Information on the tolerability of lamotrigine in epilepsy is germane to understanding the drug’s profile in BD, particularly in light of the fact that the dosage for BD is comparable with that of epilepsy.4 The exact mechanism of action of lamotrigine remains obscure. It appears to depend on voltage-sensitive sodium channels by which the neuronal membrane is stabilized and the release of excitatory neurotransmitters, such as glutamate and aspartate, is inhibited.5
Lamotrigine is also considered to have an overall favorable adverse-effect profile.
Patients receiving lamotrigine therapy have shown adverse events, mainly during the dose-escalation phase, the most common being headache, dizziness, somnolence, diarrhea, abnormal dreams and pruritus.5 Compared with the other mood stabilizing agents, lamotrigine monotherapy is associated with a lower incidence of neurological adverse events, does not cause weight gain or need close monitoring of blood levels.4
In a controlled, multicenter study of 195 patients with bipolar I disorder experiencing major depressive episode, lamotrigine monotherapy administered during a period of 7 weeks showed significant improvement in severity of symptoms when compared to placebo.5 However, in our case, the patient’s depressive symptoms became more severe, and escalated to the patient developing suicidal thoughts.
Although lamotrigine appeared sufficient to prevent mood episodes in patients with bipolar I disorder who were recently depressed, the data on the efficacy of lamotrigine in preventing suicidal ideation, suicidal attempts or death from suicide remains sparse despite its widespread use. Suicide and suicide attempts are common among patients with BD: 20% to 25% of patients attempt suicide at least once and 15% commit suicide during lifetimes.4 It is crucial that a drug prescribed for BD does not increase the risk of suicide or the incidence of suicide attempts.4
Across the 12 controlled clinical trials of lamotrigine in BD, the rates of suicide and suicidal attempts were not significant when compared with placebo.4 However, pooled analysis of 199 clinical trials of 11 different antiepileptic drugs, including lamotrigine, showed that patients randomly assigned to one of the anti-epileptic drugs had approximately twice the risk of suicidal thoughts or behaviors compared with patients randomly assigned to placebo. The increased risk was observed as early as 1 week after starting treatment with anti-epileptic drugs and persisted for 24 weeks duration, the maximum endpoint of these trials.6
The studies have confirmed the worsening of ongoing suicidal thoughts and occurrence of suicidal events while receiving lamotrigine, and the issue of the emergence of new episode of suicidal thoughts following lamotrigine initiation still remains undervalued. Considering suicidal thoughts as a dangerous event that may trigger suicidal behavior requires immediate and careful clinical evaluation. Further studies are needed to evaluate the exact danger of suicidality associated with the use of lamotrigine and guide the mental health professionals in making treatment decisions. Research studies focusing mainly on the potential of lamotrigine in provoking suicidal thoughts while controlling various confounding factors can further inform the clinician in its use in BD patients.
- Angst J. Do many patients with depression suffer from bipolar disorder?Can J Psychiatry2006; 51:3–5.
- Grunze H. The clinical side of Bipolar Disorders. Pharmacopsychiatry. 2011;44Suppl 1:S43–S48. doi:10.1055/s-0031-1275281 [CrossRef]
- The World Health Organization. The World Health Report 2001. Mental Health: New Understanding, New Hope. Chapter 2: Burden of mental and behavioral disorder. www.who.int/whr/2001/en/whr01_ch2_en.pdf. Accessed June 27, 2011.
- Nierenberg AA. An analysis of the efficacy of treatments for bipolar depression. J Clin Psychiatry. 2008;69Suppl 5:4–8. Review.
- Seo HJ, Chiesa A, Lee SJ, Patkar AA, Han C, Masand PS, Serretti A, Pae CU. Safety and tolerability of lamotrigine: results from 12 placebo-controlled clinical trials and clinical implications. Clin Neuropharmacol. 2011;34(1):39–47. doi:10.1097/WNF.0b013e3182055c07 [CrossRef]
- Highlights of Prescription information. Suicidal Behavior and Ideation. See warning and precautions (5.5). us.gsk.com/products/assets/us_lamictal.pdf. Accessed June 26, 2011.