Bipolar epidemiology
• Lifetime prevalence of bipolar disorder is ~4.5%
• 1% of patients meeting criteria for ❌, 1.1% for ❌, and 2.4% of patients with ❌ (i.e., cyclothymia, unspecified bipolar disorder)
• Symptom onset for depression, mania, or hypomania in bipolar disorder typically occurs in ❌, with >⅔ of those affected developing symptoms before ❌ years
• Depression and mixed presentations may occur more frequently in ❌
• Neuroimaging indicates that several anatomic regions (primarily the ❌ within the limbic system and the ❌ cortex) may contribute to functional abnormalities in bipolar patients
• Research suggests that altered ❌ functioning accounts for mood and cognitive changes seen in bipolar disorder, rather than dysfunction of individual neurotransmitters
• Fluctuating severity of episodes mean its up to an average of ❌ years before mood stabilisers are used

4 types of mood episodes:
1. Manic episode - abnormally elevated ❌ level. Inflated ❌, racing ❌, talking ❌, ❌ difficulty, engages in ❌ behaviors. A manic episode is differed from hypomania by ❌.
2. Major depressive episode - low ❌, anhedonia, apathy, etc.
3. Hypomania - elevated or ❌ mood, usually a ❌ duration than mania.
4. Mixed - meets criteria for ❌ manic and depressive episode

Sub-syndromal manic or depressive episodes might also occur which might not meet diagnostic criteria for one of these episodes.

• Bipolar Type I - occurrence of at least one ❌ (full mania and full depression simultaneously) episode. Typically experience major depressive episodes as well.
• Bipolar Type II – ❌ episodes.

Others:

Cyclothymic disorder - Chronic fluctuations between ❌ depressive and hypomanic episodes (2 years for adults and 1 year for children and adolescents)

Persistent depressive disorder (❌) - Depressed mood most days for at least ❌ years (1 year in children and adolescents).

❌ bipolar and related disorder - Mood states do not meet ❌ criteria

Bipolar as a spectrum:
- Type ½ - ‘Schizobipolar’ disorder: ❌ with manic, hypomanic, and depressive episodes
- Type 1 ½ - ❌, at risk for bipolar type II
- Type 2 ½ - ❌ with full ❌ episode(s)
- Type III – ❌
- Type III ½ - bipolar type 1 with ❌

• An ideal “mood stabilizer” would treat both mania and depression whilst preventing episodes of either pole, but there is as yet ❌ evidence to suggest that any ❌ agent can consistently achieve this
• Different ❌/classes effective for different ❌ of bipolar disorder
• Antidepressants either do not work, or may worsen symptoms for some (bipolar ❌) by de-stabilising mood and inducing mania or hypomania, ❌ or mixed states and possibly suicidality

Drug Txs:

1. Lithium
Narrow therapeutic range and renal toxicity therefore ❌ needed, range 0.6 - 0.75 mmol/L. Wide variation in dose required, initially ❌ daily od or bd. 80% reduced risk of ❌, possibly by decreasing impulsive-aggressive behavior. Possible MoAs: modulates ❌ proteins, affects ❌ transduction via inhibition of ❌, interferes with ❌ signal transduction cascades.

2. Valproic acid
Effective for the ❌ phase of bipolar disorder and may prevent recurrence. Not an established treatment for preventing depression but effective for some. MoA: interferes with voltage-sensitive ❌ channels by increasing inhibitory actions of ❌ and regulating downstream signal transduction cascades. Also interacts with other ion channels e.g. voltage sensitive ❌ channels, and indirectly blocks ❌.

2. Carbamazepine
Very good for acute ❌ and maintenance treatment, but is a potent ❌ inducer so generally 2nd/3rd line. MoA: Binds to ❌ subunit of voltage-sensitive sodium channels and perhaps has additional effects at calcium and potassium ion channels, to enhance the ❌ effects GABA.

3. Lamotrigine
Useful for bipolar ❌ but unlicensed - increasingly popular. Similar effects to carbamazepine on sodium channels, blocks the α subunit. Also ❌ glutamate release, which is unique. Comparatively ❌ tolerated, excluding the
propensity to cause ❌ – minimize by ❌ dose increases.

4. Atypical antipsychotics
For mania:
Established for psychotic and nonpsychotic mania. In particular, ❌. Antagonism or partial agonism of ❌, and antagonism of ❌ receptors indirectly reduces ❌, may be MoA.
For depression:
Effects ❌ receptors - indirectly disinhibits ❌ theoretically improving mood and cognition. Mood improved by blocking NA and 5-HT reuptake.

Adjunctive treatment options - ❌ for agitation; topiramate or zonisamide for weight
loss; and ❌ for anxiety, sleep, or pain

Match the unwanted effects to the drug:
❌ - propensity to cause rashes
❌ - Weight gain, sedation
❌: EPSEs, sedation, weight gain, sexual dysfunction, QT-prolongation
❌ - Weight gain, alopecia, tremor, sedation, nausea and decreased cognition, renal and thyroid function