PSY8 Bipolar disorder

Bipolar epidemiology • Lifetime prevalence of bipolar disorder is ~4.5% • 1% of patients meeting criteria for [blank_start]bipolar I[blank_end], 1.1% for [blank_start]bipolar II[blank_end], and 2.4% of patients with [blank_start]subthreshold bipolar disorder[blank_end] (i.e., cyclothymia, unspecified bipolar disorder) • Symptom onset for depression, mania, or hypomania in bipolar disorder typically occurs in [blank_start]late adolescence or early adulthood[blank_end], with >⅔ of those affected developing symptoms before [blank_start]18[blank_end] years • Depression and mixed presentations may occur more frequently in [blank_start]women[blank_end] • Neuroimaging indicates that several anatomic regions (primarily the [blank_start]amygdala[blank_end] within the limbic system and the [blank_start]prefrontal[blank_end] cortex) may contribute to functional abnormalities in bipolar patients • Research suggests that altered [blank_start]synaptic and circuit[blank_end] 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 [blank_start]8[blank_end] years before mood stabilisers are used

4 types of mood episodes: 1. Manic episode - abnormally elevated [blank_start]arousal, affect, and energy[blank_end] level. Inflated [blank_start]self-esteem[blank_end], racing [blank_start]thoughts[blank_end], talking [blank_start]quickly[blank_end], [blank_start]sleep[blank_end] difficulty, engages in [blank_start]risky[blank_end] behaviors. A manic episode is differed from hypomania by [blank_start]hospital admission[blank_end]. 2. Major depressive episode - low [blank_start]mood[blank_end], anhedonia, apathy, etc. 3. Hypomania - elevated or [blank_start]irritated[blank_end] mood, usually a [blank_start]shorter[blank_end] duration than mania. 4. Mixed - meets criteria for [blank_start]both[blank_end] 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 [blank_start]manic or mixed[blank_end] (full mania and full depression simultaneously) episode. Typically experience major depressive episodes as well. • Bipolar Type II – [blank_start]hypomanic and depressive[blank_end] episodes.

Others: Cyclothymic disorder - Chronic fluctuations between [blank_start]subsyndromal[blank_end] depressive and hypomanic episodes (2 years for adults and 1 year for children and adolescents) Persistent depressive disorder ([blank_start]Dysthymia[blank_end]) - Depressed mood most days for at least [blank_start]2[blank_end] years (1 year in children and adolescents). [blank_start]Unspecified[blank_end] bipolar and related disorder - Mood states do not meet [blank_start]full[blank_end] criteria

Alcohol and substance abuse is common (up to 50% of bipolar patients) and has a significant impact on the age of onset, course of illness and response to treatment.

5 - 15% of Bipolar II patients will develop a manic episode over a 5-year period. If this happens the diagnosis is changed to bipolar I disorder.

Choose the incorrect statement.

Bipolar as a spectrum: - Type ½ - ‘Schizobipolar’ disorder: [blank_start]Positive symptoms of psychosis[blank_end] with manic, hypomanic, and depressive episodes - Type 1 ½ - [blank_start]prolonged hypomania without depression[blank_end], at risk for bipolar type II - Type 2 ½ - [blank_start]cyclothymia[blank_end] with full [blank_start]depressive[blank_end] episode(s) - Type III – [blank_start]antidepressant induced hypomania[blank_end] - Type III ½ - bipolar type 1 with [blank_start]substance abuse-induced hypomania[blank_end]

• An ideal “mood stabilizer” would treat both mania and depression whilst preventing episodes of either pole, but there is as yet [blank_start]no[blank_end] evidence to suggest that any [blank_start]single[blank_end] agent can consistently achieve this • Different [blank_start]drugs[blank_end]/classes effective for different [blank_start]phases[blank_end] of bipolar disorder • Antidepressants either do not work, or may worsen symptoms for some (bipolar [blank_start]1[blank_end]) by de-stabilising mood and inducing mania or hypomania, [blank_start]rapid cycling[blank_end] or mixed states and possibly suicidality

Drug Txs: 1. Lithium Narrow therapeutic range and renal toxicity therefore [blank_start]TDM[blank_end] needed, range 0.6 - 0.75 mmol/L. Wide variation in dose required, initially [blank_start]0.4–1.2 g[blank_end] daily od or bd. 80% reduced risk of [blank_start]suicide[blank_end], possibly by decreasing impulsive-aggressive behavior. Possible MoAs: modulates [blank_start]G[blank_end] proteins, affects [blank_start]signal[blank_end] transduction via inhibition of [blank_start]2nd messenger enzymes[blank_end], interferes with [blank_start]downstream[blank_end] signal transduction cascades. 2. Valproic acid Effective for the [blank_start]manic[blank_end] phase of bipolar disorder and may prevent recurrence. Not an established treatment for preventing depression but effective for some. MoA: interferes with voltage-sensitive [blank_start]sodium[blank_end] channels by increasing inhibitory actions of [blank_start]GABA[blank_end] and regulating downstream signal transduction cascades. Also interacts with other ion channels e.g. voltage sensitive [blank_start]calcium[blank_end] channels, and indirectly blocks [blank_start]glutamate[blank_end]. 2. Carbamazepine Very good for acute [blank_start]mania[blank_end] and maintenance treatment, but is a potent [blank_start]CYP3A4[blank_end] inducer so generally 2nd/3rd line. MoA: Binds to [blank_start]alpha[blank_end] subunit of voltage-sensitive sodium channels and perhaps has additional effects at calcium and potassium ion channels, to enhance the [blank_start]inhibitory[blank_end] effects GABA. 3. Lamotrigine Useful for bipolar [blank_start]depression[blank_end] but unlicensed - increasingly popular. Similar effects to carbamazepine on sodium channels, blocks the α subunit. Also [blank_start]decreases[blank_end] glutamate release, which is unique. Comparatively [blank_start]well[blank_end] tolerated, excluding the propensity to cause [blank_start]rashes[blank_end] – minimize by [blank_start]slow[blank_end] dose increases. 4. Atypical antipsychotics For mania: Established for psychotic and nonpsychotic mania. In particular, [blank_start]quetiapine and aripiprazole[blank_end]. Antagonism or partial agonism of [blank_start]D2 hyperactivity[blank_end], and antagonism of [blank_start]5-HT2A[blank_end] receptors indirectly reduces [blank_start]glutamate hyperactivity[blank_end], may be MoA. For depression: Effects [blank_start]5HT2A, 5HT2C, & 5HT1A[blank_end] receptors - indirectly disinhibits [blank_start]NA and DA neurons[blank_end] theoretically improving mood and cognition. Mood improved by blocking NA and 5-HT reuptake. Adjunctive treatment options - [blank_start]benzodiazepines[blank_end] for agitation; topiramate or zonisamide for weight loss; and [blank_start]gabapentin or pregabalin[blank_end] for anxiety, sleep, or pain

Match the unwanted effects to the drug: [blank_start]Lamotrigine[blank_end] - propensity to cause rashes [blank_start]Valproic acid[blank_end] - Weight gain, sedation [blank_start]Atypical antipsychotics[blank_end]: EPSEs, sedation, weight gain, sexual dysfunction, QT-prolongation [blank_start]Lithium[blank_end] - Weight gain, alopecia, tremor, sedation, nausea and decreased cognition, renal and thyroid function