HALF-LIFE: 25-33 hours
>With valproic acid: 48-70 hours
>With Carbamazepine: 13-14 hours
STARTING DOSE: 25mg PO daily
TARGET DOSING RANGE: 50mg-200mg per day
BEST TIME TO DOSE: Any (causes insomnia in some patients)
HOW TO DOSE:
If dosing without valproic acid:
>Initial 25mg PO Daily for two weeks
>Increase to 25mg PO BID for two weeks
>Increase to 50mg PO BID for two weeks
>If tolerated, can consolidate to once daily dosing
>Max dose without valproate typically 200mg per day
If dosing with valproic acid:
>Initial 25mg PO every other day for two weeks
>Increase to 25mg PO daily for two weeks then 50mg PO daily
>Max dose with valproate typically 100mg per day
*RESTART TITRATION IF STOPPED/MISSED FOR >5 HALF LIVES*
PREGNANCY: Minimal data on safety in humans. Must weigh risk of discontinuing vs risk of teratogenicity (which is low)
BREASTFEEDING: Minimal data on safety in humans. Recommend bottle/formula feeding
1) Bipolar Disorder (maintenance/preventing mood episodes)
2) Seizures in adults and children
- Lamotrigine shows prophylactic and antidepressant properties, but is no better than placebo in treating mania
- Lamotrigine has been shown to reduce glutamate release and modulate reuptake of monoamines including serotonin and dopamine
- Lamotrigine has been shown to increase the time between both depressive and manic episodes
- May be a good add-on medication with lithium for bipolar depression
- Mostly case reports and open labeled trials support lamotrigine in rapid cycling bipolar disorder, bipolar depression, and mixed episodes but RCTs have not consistently demonstrated efficacy for these conditions
- Lamotrigine carries a risk of both benign rash and Steven Johnson’s Syndrome/TEN
- Rash associated with rapid dose escalation
- Reduce dose and slow titration if benign rash develops
- Discontinue if SJ/TEN (obviously)
- Interaction between valproic acid and lamotrigine
- Valproic acid inhibits lamotrigine metabolism
- Dose of lamotrigine must be decreased by half the normal dose when given in combination with valproic acid
- Many hormonal contraceptives decrease lamotrigine levels
- Caution during contraceptive-free “pill-free” periods as lamotrigine levels may rise substantially
- Conversely, lamotrigine may decrease levels of hormonal contraceptives
- Carbamazepine decreases lamotrigine levels
- Metabolism of lamotrigine primarily hepatic but not by CYP450 system
- If lamotrigine stopped/missed for >5 half-lives then strongly consider restarting titration
INFORMATION ABOUT MOOD DISORDERS
What Does “Mood” Mean?
Mood is defined as a person’s internal emotional state that is sustained over time. Mood is subjective and experienced by the person. Terms used to describe mood: Normal, Sad, Angry, Irritable, Anxious, Happy
What Does “Affect” Mean?
Affect is a term used to describe the outward expression of a mood state. In other words, an individual’s affect is visible to others. Healthcare providers obtain important information about an individual’s internal emotional experience (mood) based on their emotional expression (affect). Terms used to describe an individual’s affect: Dysphoric, Happy, Excited, Irritable, Angry, Tearful, Blunted, Euthymic, Flat, Blunted, Constricted, Restricted, Appropriate, Congruent.
What Are Mood Disorders?
Mood disorders are group of psychiatric disorders in which disturbances of mood or affect are severe and persistent enough to cause significant problems in an individual’s life. Moods by themselves are not pathological and many of us have experienced a wide range of mood states. When moods become severe and persistent enough to cause dysfunction and issues in an individual’s life, then we use the term “mood disorder.” Mood disorders are better defined as syndromes consisting of a cluster of signs and symptoms that often “come and go” in “episodes” which persist for weeks, months, or even years. During these “episodes,” there is a significant change in the individual’s mood which may negatively impact work performance, relationships, or other important areas of functioning. The most common mood disorder is major depressive disorder (MDD), often referred to as “Unipolar depression.” Bipolar disorders are also mood disorders that differ from unipolar depression by the presence of elevated mood states called hypomania or mania.
What is Mania?
Mania is characterized by a distinct period of abnormally and persistently elevated, expansive, or irritable mood and abnormally and persistently increased goal-directed activity or energy, lasting at least 1 week and present most of the day, nearly every day (or any duration if hospitalization is necessary). During this period of elevated/expansive mood/energy, individuals may experience any combination of the following: Inflated self-esteem or grandiosity; Decreased need for sleep (e.g., feels rested after only 3 hours of sleep); More talkative than usual or pressure to keep talking; Flight of ideas or subjective experience that thoughts are racing; Distractibility (i.e., attention too easily drawn to unimportant or irrelevant external stimuli), as reported or observed; Increase in goal-directed activity (either socially, at work or school, or sexually) or psychomotor agitation (i.e., puroseless non-goal-directed activity); Excessive involvement in activities that have a high potential for painful consequences (e.g., engaging in unrestrained buying sprees, sexual indiscretions, or foolish business investments). As with any “disorder,” the mood disturbance is sufficiently severe to cause marked impairment in social or occupational functioning or to necessitate hospitalization to prevent harm to self or others, or there are psychotic features. If the mood disturbance can be attribute dto a drug, medication, or medical condition then the term “manic episode” should not be used.
What is Hypomania?
Hypomania is a less severe form of mania and is characterized by a distinct period of abnormally and persistently elevated, expansive, or irritable mood and abnormally and persistently increased activity or energy, lasting at least 4 consecutive days and present most of the day, nearly every day with the same symptoms that characterize mania (see above).
Subtypes of Bipolar Disorder:
Bipolar 1 Disorder: Manic or Mixed episode +/- Major Depressive Episode (Only manic episode required)
Bipolar 2 Disorder: Hypomanic episode + Major Depressive Episode (both are required)
With rapid cycling: 4 or more mood episodes in a 12-month period
Neurobiology of Bipolar Disorder
The underlying biochemical abnormalities that cause or contribute to bipolar disorder remain unclear. However, studies have suggested neurobiological differences between unipolar and bipolar depression which is further supported by the relative lack of efficacy of classic antidepressant monotherapy in the treatment and prevention of bipolar depression. Human studies have found increased concentrations of noradrenaline (norepinephrine) and dopamine (DA) and decreasedconcentrations of serotonin (5-HT) in manic patients which suggests that norepinephrine and dopamine dysregulation may play a primary role in manic symptoms. In patients with unipolar depression, both serotonin (5-HT) and norepinephrine concentrations are low. Perhaps the imbalance partially explains bipolarity? Lastly, glutamate and GABA dysregulation have been implicated in the pathophysiology of bipolar disorder. Animals studies suggest increased glutamatergic neurotransmission via NMDA receptors in manic patients. In addition, the efficacy of anticonvulsants and benzodiazepines in the treatment of bipolar disorder suggests the likelihood that glutamate and GABA systems are involved in uncertain ways.
It is likely that the combination of vulnerable genetics and environmental stressors lead to intracellular changes in transcription, signal transduction, and synaptic functioning that ultimately give rise (via poorly understood mechanisms) to symptoms of bipolar disorder.
Functional Imaging Studies
Functional Connectivity Studies have demonstrated or suggested
(1) Decreased connectivity between the amygdala and anterior cingulate cortex
(2) Increased connectivity between the amygdala and the supplemental motor area
Functional Neuroimaging Studies have demonstrated or suggested
(1) Decreased size and activity in the PFC of patients with bipolar disorder—similar to that found in patients with unipolar depression.
(2) Increased gray matter volume in bipolar patients after 4 weeks of lithium treatment (Note: Valproic acid (depakote) has not been shown to have the same effect.
(3) Amygdala are larger and more active in the bipolar patients.
(4) Bipolar disorder may be the result of abnormal interactions between the PFC and subcortical regions such as the amygdala—an abnormality not usually seen with unipolar depression.
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