Unit 9: Mood Stabilizers Flashcards
Drugs for bipolar disorder - lithium - valproate - lamotrigine - carbamazepine
Mood Disorders
Major Depressive Disorder (MDD) (unipolar depression)
- chronic depressed mood
- fatigue, avolition, anhedonia, changes in appetite and sleep, rumination, suicidality
- comorbid with anxiety disorders
- high lifetime prevalence (approx. 15-20%)
Bipolar Disorder (bipolar depression)
- alternations between mania and depression
- broad onset (from early adolescence - young adulthood)
- often accompanies psychological trauma (verbal; physical; sexual violence)
- periods of suicidal thoughts/intent
Bipolar Types
The main difference between the types is the severity of symptoms:
Bipolar Type 1
- primarily experience longer/more severe periods of mania
- may or may not have depressive episodes
Bipolar Type 2
- recurrent depression accompanied by periods of hypomania
- hypomania (milder state of mania) — symptoms do not cause impairment in social/occupational functioning or a need to be hospitalized, but are still observed by others
Cyclothymic Disorder
- rare mood disorder
- rapid cycling of emotional highs and lows—fluctuating between hypomanic and depressive states
- not as extreme as bipolar, thus does not meet the BD diagnostic criteria
Mania
Mania: a distinct period of abnormally and persistently elevated, expansive or irritable mood, lasting at least 1 week (or any duration if hospitalization is necessary)
- a chemical imbalance in the brain—linked to an over-excitation of various brain regions/neurons (eg: noradrenaline)
- without treatment, mania can cause structural changes in the brain that are detrimental for cortical integrity:
- neurodegeneration,
- neurotoxic susceptibility,
- neuronal apoptosis (neuronal cell death),
- altered neuroplasticity caused by neuroinflammatory processes and/or oxidative stress during mood episodes
- triggers:
- sleep-deprivation
- changes to sleep routine
- life stress (positive and negative)
- changes to daily routine
- substance abuse (particularly of stimulants like amphetamine)
Mania DSM-V Criteria
Mania Criteria: lasting at least one week (any duration if hospitalization is required)
(1) Grandiosity — increased self-esteem, feeling invincible/superior to others
(2) Sleep — decreased need for sleep
(3) Speech — more talkative than usual or pressure to keep talking
(4) Flight of Ideas — racing thoughts
(5) Distractibility — attention too easily drawn to unimportant or irrelevant external stimuli
(6) Motivation — increase in goal-directed activity (either socially, at work or school, or sexually) or psychomotor agitation
(7) Impulsivity — spontaneous or excessive involvement in pleasurable activities that have a high potential for painful consequences (eg: unrestrained spending sprees, sex, foolish investments, etc.)
Depression DSM-V Criteria
Depression Criteria: 5/9 symptoms for a minimum of two weeks
(1) Low Mood — depressed mood for most of the day
(2) Anhedonia — diminished interest or pleasure in all or most activities
(3) Apathy — lack of energy or motivation
(4) Weight — significant unintentional weight loss or gain
(5) Movement — noticeable agitation or psychomotor retardation
(6) Low Energy — fatigue or loss of energy
(7) Rumination — feelings of worthlessness or excessive guilt
(8) Brain Fog — diminished ability to think or concentrate, or indecisiveness
(9) Suicidality — recurrent thoughts of death and suicide
Bipolar Disorder Epidemiology
Bipolar Epidemiology
Genetic
- genetic factors account for 70-80% of bipolar’s cause
- heritability: if one parent has BP, child has 10% risk of developing
- genetic susceptibility for BP disorder shares more in common with schizophrenia than unipolar depression (MDD)
Environmental
- stressful life events (grief, loss of job, new baby, moving, etc.)
- abuse/trauma
- subtance/alcohol abuse
Bipolar Disorder Demographics
Bipolar Disorder Demographics
WHO
- equal prevalence between males and females—estrogen≠protective (unlike in schizophrenia)
WHAT
- a mood disorder characterized by episodes of high and low mood (depression and mania/hypomania)
- progressive: illness can worsen without treatment
WHEN
- onset: early adolesence - early adulthood
WHERE
- globally presented
- lifetime prevalence 1-2%
WHY
- strong genetic component (accounting for 70-80% of the cause)
- environmental factors also play a role
Bipolar Comorbidities
Bipolar Comorbidities:
- ADHD
- anxiety disorders
- substance abuse
- obesity
- metabolic syndrome—T2D, cardiovascular disease, dyslipidemia (high cholesterol)
- suicide
- thoughts — 80%
- attempts — 50%
- complete — 15%
Bipolar Disorder Treatment
Bipolar Disorder Treatment
- treatment is complex, generally involving a mix of:
- (1) mood stabilizers
- (2) antidepressants
- (3) antipsychotics
- lifestyle changes and psychotherapy are important aspects of BP disorder treatment
- illness will progressively worsen without treatment
Bipolar Disorder Treatment:
(1) Mood Stabilizers
(1) Mood Stabilizers: drugs that attenuate the high of mania and the low of depression
(A) mineral mood stabilizers
- (a) lithium
(B) anticonvulsant mood stabilizers
- (b) valproic acid
- (c) lamotrigine
- (d) carbamazeprine
Treatment: (1) Mood Stabilizers
(A) Mineral Mood Stabilizers
(A) Mineral Mood Stabilizers
(a) Lithium
- discovered by accident
- lithium salt—(lithium carbonate) previously added to salt as a supplement, was removed due to nephrotoxicity (kidney tox)
- most effective mood stabilizer
Target: unknown
MOA: also unknown; thought to antagonize GSK-3 enzyme—responsible for passing along chemical signal after dopamine receptor activation—(blocks downstream signalling events)
- works inside postsynaptic neuron cell
- similar effects as antipsychotics (blocking D2 receptors)
- prevents mania without causing the adverse effects of APS (eg: anhedonia)
- limitations:
- narrow therapeutic window
- 30% of patients are “lithium resistant”
Lithium Adverse Effects
Lithium Adverse Effects
ACUTE
- dry mouth
- metallic taste
- frequent urination
- shaky hands
- acute toxicity (from the wrong dose/due to narrow therapeutic window)
- emesis
- confusion
CHRONIC
- thyroid issues
- insufficient thyroid hormome production
- kidney toxicity
- damage/cysts
- renal failure
Treatment: (1) Mood Stabilizers
(B) Anticonvulsant Mood Stabilizers
(B) Anticonvulsant Mood Stabilizers
(b) Valproic acid (valproate)
- also treatment for epilepsy
Target: unknown
MOA: also unknown—appears to have many functions in preventing seizures and manic episodes:
- (1) antagonizes voltage-gated sodium channels
- sodium channels are required to propagate action potentials along the axon
- lidocaine/cocaine also antagonize these channels
- (2) changes gene expression and increases the amount of GABA (inhibitory neurotransmitter) produced
- function of this for bipolar disorder treatment is unknown
(B) Anticonvulsant Mood Stabilizers
(c) lamotrigine and (d) carbamazepine
- also approved for treating epilepsy
- multiple targets
Target: unknown
MOA: also not fully known (like valproate)—appear to antagonize glutamate receptors and calcium channels
- reduces axon/neuron firing
- (c) lamotrigine = depressive mood stabilizer
- (d) carbamazepine = manic mood stabilizer
Bipolar Disorder Treatment:
(2) Antidepressants
(3) Antipsychotics
(2) Antidepressants
- used to treat bipolar disorder ONLY IN COMBINATION with a mood stabilizer or antipsychotic
- using antidepressants on their own can trigger mania in patients with BP disorder
(3) Antipsychotics (2nd gen)
Quetiapine
- may be used alone since it seems to have some anti-depressant properties in the treatment of bipolar disorder (in addition to APS effects)
Major Depressive Disorder (MDD) (unipolar depression)
- chronic depressed mood
- fatigue, avolition, anhedonia, changes in appetite and sleep, rumination, suicidality
- comorbid with anxiety disorders
- high lifetime prevalence (approx. 15-20%)
*Depression Criteria**: 5/9 symptoms for a minimum of two weeks
(1) Low Mood — depressed mood for most of the day
(2) Anhedonia — diminished interest or pleasure in all or most activities
(3) Apathy — lack of energy or motivation
(4) Weight — significant unintentional weight loss or gain
(5) Movement — noticeable agitation or psychomotor retardation
(6) Low Energy — fatigue or loss of energy
(7) Rumination — feelings of worthlessness or excessive guilt
(8) Brain Fog — diminished ability to think or concentrate, or indecisiveness
(9) Suicidality — recurrent thoughts of death and suicide
