Week 8: Mental health - Depression, Sleep and Anxiety, Bipolar Disorder, Schizophrenia Flashcards
Depression or Major Depressive Disorder (MDD)
- Definition
- Clinical symptoms for diagnosis
MMD
- One of the affective disorders or disorders which affect mood
- Degree of depression that interferes with daily functioning (not situational depression)
Diagnostic clinical symptoms (present for at least 2 weeks and impair daily functioning)
- Lethargy
- Depressed mood
- Loss of interest; personal neglect
- Weight loss; appetite loss
- Insomnia or hyper-somnolence
- Feelings of worthlessness
- Suicidal ideation
MDD risk factors
- 25% is genetic
- More common in first world countries
- Slightly higher rate in women
- Postnatal depression affects 10-20% mothers
- Most common in 18-24 yrs
- In older patients, significant higher with coexisting illness such as CHD/stroke, diabetes, cancer, RA, osteoporosis
MDD pathophysiology - neurotransmitters involved
- Original theory
- Current theory
Originally thought to be caused by defecit in neuronal signalling of serotonin and noradrenaline with low amounts in synaptic cleft leads to inefficient signalling and depressed state
Now know that it is more complex and involves other neurotransmitters including dopamine and glutamate as well as brain derived neurotropic factor and hormones cortisol and melatonin
MOA of neurotransmitter signalling
- Monoamines (5HT, DA and NA) are synthesized and stored in presynaptic nerve vesicles and released into synaptic cleft
- Diffuse across cleft and interact with postsynaptic neuron receptor, which leads to physiological response
- Any excess monoamines are either degraded by monoamine oxidase (MAO) or catechyl-o-methyltransferase (COMT) into synaptic cleft or go back into presynaptic neuron via reuptake transporters and degraded in presynaptic neuron by MAO/COMT
MMD treatment
- Lifestyle and individualisation
Treatment should always include - Lifestyle (reduce stress, healthy diet and exercise) - CBT - Cease illicit drugs and alcohol Treatment is very individualized - History of success/failure with treatment - Concurrent illness - Other medication - Likelihood of deliberate overdose - Tolerable ADR
MMD pharmacotherapy treatment: Tricyclic antidepressant (TCA) - MOA - ADR - Examples
- One of the first developed
MOA
- Block presynaptic reuptake of 5HT, NA and DA
- Also blocks receptors in periphery leading to unwanted effects
Adverse effects (lots - not extensive)
- Dry mouth
- Blurred vision/dizziness/orthostatic hypotension
- Constipation
- Tachycardia
- Confusion
- Sedation
- Reduced seizure threshold
- Weight gain
It is toxic and fatal in overdose
Example
- Amitriptyline
- Imipramine
- Nortiptyline
MMD pharmacotherapy treatment:
Tricyclic antidepressant (TCA)
- Contraindications and cautions
Pregnancy
- May increase malformation or premature delivery
Hepatic impairment
- May increase concentration to toxicity
- Half dose
Geriatric
- May have slower response
- Increase risk of fall
Not to be used in patients with suicidal idealizations, epilepsy or within 14 days of stopping MAOI
Children
- Not to be used unless under specialist
MMD pharmacotherapy treatment: Selective serotonin reuptake inhibitor (SSRI) - MOA - ADR - Overdose - Examples
MOA
- Selectively block presynaptic reuptake of 5HT
Adverse effects
- More specific therefore less ADR than TCA
- Hyponatremia especially in elderly
Overdose
- Toxic (not as toxic as TCA)
- Seratonin toxicity causing increased temp, agitation, tremor, palpitations, sweating, diarrhea, mania
Examples
- Citalopram/Escitalopram
- Fluoxetine
- Sertraline
MMD pharmacotherapy treatment:
Selective serotonin reuptake inhibitor (SSRI)
- Contraindications and cautions
Those at high risk of bleeding
- Monitor for hyponatremia
Children
- Evidence weak
- May use fluoxetine with specialist supervision
Pregnancy - Category C - May cause premature delivery or infant withdrawal Breastfeeding - Use sertraline
Not to be used within 14 days of stopping MAOI due to serotonin toxicity
Hepatic
- Reduce dose in hepatic impairment
MMD pharmacotherapy treatment: Serotonin and Noradrenaline reuptake inhibitor (SNRI) - MOA - ADR - Examples
MOA
- Block presynaptic reuptake of both 5HT and NA
Adverse effects
- Similar to SSRI but nore due to NA blocking (more cardiac ADR)
- BP monitoring regularly
- Caution in patients with heart disease
- Contraindicated in recent MI or uncontrolled BP/arrhythmia
- Serotonin syndrome still a risk
- Contraindicated in patient with high risk of bleeds
- May lower seixure threshold
- Not associated with weight gain
Examples
- Venlafaxine
- Desvenlafaxine
- Duloxetine
MMD pharmacotherapy treatment:
Serotonin and Noradrenaline reuptake inhibitor (SNRI)
- Contraindications and cautions
High risk of bleeding
- Monitor for hyponatremia
Not to be used within 14 days of stopping a MAOI due to serotonin toxicity
Contraindicated in patients with unstable heart disease or hypertension
Pregnancy - Category C - Infant withdrawal likely Breastfeeding - Concentration in milk lower but needs monitoring
Hepatic impairment
- Reduce dose
MMD pharmacotherapy treatment: Non selective monoamine oxidase inhibitor (MAOI) - MOA - ADR - Examples
MOA
- Non selective and irreversible block MAO-A and MAO-B from breaking down 5HT, NA, adrenaline and DA
Adverse effects
- Many
- Weight gain
- Sleep disturbance
- Impotence
Examples
- Phenelzine
- Tranylcypromine
MMD pharmacotherapy treatment:
Non selective monoamine oxidase inhibitor (MAOI)
- Contraindications and cautions
Elderly
- Use with caution due to hypotension and CVD risk
- Half starting dose
Pregnancy
- No data; seek specialist
Breastfeeding
- No data; seek specialist
Must separate from other antidepressants/serotonergics by 14 days
Do not use in patients with CHD, epilepsy, diabetes or angina
Monitor BP
Hepatic
- Avoid use in significant liver disease
MMD medication changes
- Start low and go slow
- Gradual withdrawal
- Check AMH changeover guide for time clearance before starting new drug
MMD Treatment Practice points
- All drugs take weeks to see effect (2-3 weeks for any difference and 6+ weeks for full effect)
- Sometimes things seem worse before they get better (suicidal idealization increases in first weeks)
- Cannot stop once they feel better due to higher rate of relapse if sudden termination, most continue for at least 6-12 months after symptoms resolve
- Some patients are on medication for life
Bipolar disorder definition
- What is mania?
Bipolar disorder is when patients experience bouts of clinical MMD interspersed with manic episodes
Mania
- Expansive or irritable mood
- Inflated self esteem
- Decreased need for sleep
- Rapid long speech
- Racing thoughts/inability to concentrate
- Impulsive behavior/dis-inhibition
- Aggression/violence
- Excessive involvement in pleasurable activities (poor judgement)
Causes of bipolar disease
- Difficult to treat and more severe than MMD with over 90% experiencing relapse
- Onset early adlthood
- Can be caused by drug therapy (antidepressant, anti-parkinson’s, corticosteroids)
Bipolar disorder - Acute mania
Acute mania is a medical emergency
- Delusions, impaired judgement, aggression, violence, psychosis
- Usually hospitalized
- Treated with mix of antipsychotics and anxiolytic medication under close supervision
Bipolar disorder - Treatment/Prophylaxis
Most patients treated with same 1st line option antidepressants as in MMD
- At incorrect dose can cause mania
- Monitor closely
- Withdrawn once depression resolves
- Also consider CBT and ECT
Bipolar disorder - treatment
- Quetiapine
- First line option
- Antipsychotic - blocks DA transmission in brain
- Lots of interactions/contraindications/ADR
- Works to control both depression and mania
Bipolar disorder - Prophylaxis
- Lithium
- MOA
- Toxicity
- 1st line for prophylaxis (2 or more episodes or severe first episode)
MOA
- Largely unknown
- Inhibits DA release to help control impulsive behavior and disinhibition
- Enhances 5HT release
- Does not have any effect in normal individuals
Narrow therapeutic window = monitor
Toxicity
- Vision changes, GI upset, drowsiness, flu like symptoms, muscle weakness
- Advance toxicity (muscle rigidity, seizure like movements, tremors, disorientation, seizure, psychosis, coma
Bipolar disorder - Prophylaxis
- Lithium
- Contraindications and ADR
Contraindicated
- Thyroid issues
- Psoriasis
- Renal impairment
- Elderly - monitor and reduce dose as renal failure and hyponatremia are high risk
- Pregnancy - avoid in 1st trimester
ADR
- Watch sodium levels due to dehydration, fasting before/after surgery and illness
- GI effects
- Weight gain
- Skin problems
- Memory impairment
