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
Bipolar disorder - Prophylaxis
- Anti-epileptics
Sometime used for prophylaxis of bipolar
- Beyond scope
- Don’t know how they work for bipolar
- Used in combination with lithium
Anxiety
- Primary
- Secondary
- First line treatment
- Goals of therapy
Primary
- No underlying cause
Secondary
- Caused by another condition/drug therapy
First line therapy for all anxiety
- Psychological therapy (coping mechanism, stress reduction, counseling, breathing control)
Goals of therapy
- Control symptoms
- Improve social functioning
Types of anxiety and their features
Panic attack
- Short lived
- Rapid onset
- Intense fear/discomfort
- Sweating, palpitation, trembling, nausea, chest pain, dizziness, tingling, chills/flush
Generalized anxiety disorder (GAD)/Panic disorder
- Excessive anxiety over time and across number of events
- Occur more days than not over 6 months
- Anticipatory anxiety, elevated general tension, preoccupation, phobic avoidance, insomnia, irritability, loss of concentration, muscle tension
Post traumatic stress disorder
- Anxiety secondary to traumatic event involving risk of death or serious injury
- Response involved fear/helplessness/horror
- Flashbacks, exaggerated startle response, irritability, anger, avoidance, mood changes, depression
Obsessive Compulsive disorder (OCD)
- Anxiety/distress with recurrent and persistent thoughts that are intrusive and inappropriate which are products of own mind
- Results in repetitive, ritualized behavior to reduce anxiety
Specific phobia
- Unreasonable and persistent fear triggered by either presence or anticipation of situation/object
- 5 classes (animals, natural, blood/injury, situational or other)
Benzodiazepines
- MOA
- Effects when activated
- Adverse effects
MOA
- Act to potentiate effect of GABA on GABA receptor
- GABA is inhibitory meurotransmitter fought throughout CNS and inhibits neuronal firing
Effects when activated
- Anxiolytic
- Sedative
- Hypnotic
- Muscle relaxant
- Antiepileptic
Adverse effects
- Drowsiness/over sedation
- Light headedness/dizziness/vertigo
- Blurred vision
- Memory loss/retrograde amnesia
- Hyper salivation
- Slurred speech
- Headache
- Respiratory depression
- Decreased libido
- Hypotension
Benzodiazepenes
- Contraindications and cautions
Elderly
- High risk of sedation, ataxia, confusion, falls and respiratory depression
- Lower dose, short term, short acting
Children
- Avoid due to greater sensitivity to CNS effects
- May be given short term by specialist
Pregnancy
- 1st and 2nd trimesters use low dose, short acting
- Avoid in 3rd trimester
Breastfeeding
- Monitor for sedation
Hepatic
- Contraindicated in severe hepatic impairment
- Use low dose short acting in mild impairment
Renal
- Use lower initial dose
Contraindicated in history of alcohol or drug abuse - high risk of dependence and abuse
Contraindicated in those suffering from sleep apnoea
Benzodiazepines
- Practice points
- Start low, go slow
- Gradual withdrawal due to withdrawal effects or irritability, insomnia, sweating, hallucinations, HT and tachycardia, psychosis/seizure
- Highly addictive - low dose, shortest acting for shortest possible time
Anxiety (GAD) Pharmacotherapy
- Indicated if symptoms are causing significant distress and disruption to daily life and psychological therapy not controlling well
- Start low and go slow
- Use antidepressants as preferred therapy
- Use benzodiazepines for short term initial control or panic attack onset while wait for antidepressants to take effect
Anxiety (OCD) Pharmacotherapy
Best drugs for OCD effect the serotonergic system
- SSRI
- TCA
Doses are usually higher than in depression
Definition of:
- Obsession
- Anxiety
- Compulsion
- Relief
Obsession
- Unwanted distressing thought, urges, mental images
- May include what if? and doubts
Anxiety
- May be distress, fear, worry or disgust
- Its a false alarm
- Feel the need to do something
Compulsion
- Any behavior performed to help make the anxiety go away
Relief
- Only temporary
- Obsession come back
Types of sleep disorders
- Insomnia
- Sleep terror/Sleep walking
- Restless leg syndrome
- Jetlag
- Narcolepsy
Stages of sleep
Stage 1
- 4-5%
- Light sleep
- Muscle activity slows
- Occasional muscle twitch
Stage 2
- 45-55%
- Breathing pattern and HR slow
- Slight decrease in body temp
Stage 3
- 4-6%
- Deep sleep begins
- Brain begins to general slow delta waves
Stage 4
- 12-15%
- Very deep sleep
- Rhythmic breathing
- Limited muscle activity
- Brain produces delta waves
Stage 5
- 20-25%
- Rapid eye movement
- Brainwaves speed up and dreaming occurs
- Muscle relax and heart rate increase
- Breathing is rapid and shallow
Insomnia
- Pathophysiology
- Classification
- Not well understood
- Does involve physiological mechanisms, cognitive mechanisms, cortical arousal
- When sleep cycle disrupted, leading to clinically significant effects on lifestyle for at least 1 month it is classified as insomnia
Sleep disorders - non pharmacological therapy
Non pharm is first line for sleep disorders
- Remove underlying cause (drug/alcohol/prescription
- CBT/meditation/stress management
- Sleep hygiene
- Consistent sleep wake times
- Reduce caffeine/stimulants
- Remove stimuli from room
- Regular exercise
- No eating/exercising close to bed
- Meditation/breathing/stretching before bed
- Get out of bed and do something if not sleeping within 20 min
Insomnia - pharmacotherapy options
Benzodiazepines
- Potentiate inhibitory effect of GABA (sedating effect - remove anxiety of not sleeping)
Zolpidem
- Potentiates inhibitory effect of GABA
- Stronger than benzodiazepines - more side effects
Melatonin
- Works to reset circadian rhythm
- Produced naturally in response to low light levels, tells hypothalamus its time for sleep
- Useful in jetlag
Zolpidem (Insomnia)
- Contraindications and cautions
Elderly
- High risk of sedation, ataxia, confusion, fall and respiratory depression
- Low dose for as short term as possible
Children
- Not recommended
Pregnancy
- Category B3
Breastfeeding
- Seek specialist advice
Hepatic
- Use lower dose in mild to mod impairment
- Avoid in severe impairment
Contrainidicated
- History of alcohol or drug abuse due to high risk of dependence or abuse
- Concomitant alcohol intake
Melatonin (insomnia)
- Contraindications and cautions
Elderly
- Good efficacy >55 yrs
Children
- Not recommended
Pregnancy
- Category B3
Breastfeeding
- Seek specialist advice
Hepatic
- Contraindicated in hepatic impairment
What is the role of dopamine in sleep?
DA increases alertness in hypothalamus
- Any drug increases effect of DA in hypothalamus promotes wakefulness
- Any drug inhibit DA in hypothalamus may cause drowsiness
Narcolepsy
- What is it
- How to treat
Narcolepsy
- Fall asleep inappropriately
Treatment
- Require stimulants to keep them awake
- Amphetamines which increase 5HT, NA, DA in cleft therefore increase neurotransmitter and promote wakefulness
Restless leg syndrome
- Pathophysiology
- Treatment
RLS
- Product of reduced DA transmission in substantia nigra which controls movement
Treatment
- DA agonists to increase DA transmission and restore normal movement
Schizophrenia
- Symptoms and presentation
- Disturbed speech
- Altered perception
- Cognitive decline
- Emotional disturbance
- Disturbed volition (willpower)
Years before clinical onset may experience changes in cognition, motor skills, language, social skills, behavior
Summary of symptoms
- Positive (hallucinations, delusions, impaired sight, disorganized thinking and speech
- Negative (lack motivation, poor self care, blunted affect, reduced speech output, social withdrawal)
- Cognitive (impaired planning, reduced mental flexibility, impaired memory, impaired social cognition)
- Excitement (disorganized behavior, aggression, hostility)
- Mood (depression, anxiety)
Schizophrenia - Stages of illness (disease progression)
Premorbid (Until puberty)
Prodromal (early 20’s)
Onset/deterioration (20-30)
Chronic/residual (35+)
Schizophrenia - Causes
Still largely unknown
- Genetic factors
- Environmental factors (exposure during pregnancy - infant hypoxia is also strongly linked)
- Changes is size and neuronal activity in certain parts of brain are significantly different in schizophrenia
Schizophrenia
- The dopamine hypothesis
- Effect of serotonin
Dopamine hypothesis
- Proposes that schizophrenia is caused by excessive dopamine in brain
- Leads to DA receptor function defects
- Evidence
> Chlorpromazine was 1st antipsychotic (post synaptic D2 antagonist)
> Drugs that increase dopamine release increase psychotic symptoms (Cocaine, LSD, amphetamines, D2 agonists)
Serotonin
- 5HT neurons are structurally similar to DA and tend to innervate same areas in brain
- Schizophrenia patients have higher 5HT blood levels
- 5HT receptors are present on DA neurons (may increase or decrease DA release)
> In some DA pathways 5HT blocks release of DA such as nigrostriatal (movement)
Schizophrenia non pharmacotherapy treatment
- Counseling
- Family support
- Intensive psycho-social interventions
Schizophrenia pharmacological treatment
Antipsychotics
- Prevent relapse
- Reduce positive/excitement symptoms
- Not all effective for controlling negative symptoms, cognitive impairment and mood disturbances (require additional therapy)
Classification of antipsychotics
First method = Generation
- First and second generation antipsychotics
Second method = Typicals
- Typical and atypical antipsychotics (refers to which receptors blocked)
MOA of antipsychotics
Antipsychotic actions are thought to be mediated by blockade of dopaminergic transmission in various parts of brain (particularly limbic system)
All effective antipsychotics block D2 receptor
- Antagonism of other receptor may influence antipsychotic activity
Antipsychotics - D2 receptor blockade
- Adverse effects that result
Blocking D2 receptor does not only reduce the positive symptoms of schizophrenia; it also results in a variety of serious side effects due to changing DA transmission in CNS
- Extrapyramidal side effects (EPSE) include movement issues
> Dystonias = muscle spasm in head and neck, can result in stiffening due to cholinergic receptor activation
> Akathisia = feeling motor restlessness
> Parkinsonism = tremor/rigidity/slow voluntary movement
> Tardive dyskinesia = involuntary movement of face/mouth/tongue/head/neck/limbs
- Cardiovascular
> Lengthen QT interval
> Orthostatic hypotension
> Increase risk of VTE
- Metabolic
> Weight gain
> Increase blood glucose
> Dyslipidaemia
- Anticholinergic
> Urinary retention/constipation
> Dry eye/mouth
> Tachycardia
Benefit of atypical antipsychotics
Atypical antipsychotics are newer drugs that have lower risk of EPSE due to also blocking certain 5HT receptors
- Allows some dopamine signalling within movement areas of brain rather than complete block of receoptors
Anipsychotic - Halperidol
- Type of antipsychotic
- Contraindications and cautions
Older, typical antipsychotic
Elderly
- Higher risk for stroke
- May increase confusion, hypotension, anticholinergic effects and acute EPSE
Children
- Highest risk of Tardive dyskinesia
- At risk for metabolic abnormalities and learning difficulties
Pregnancy
- Individualized based on risk/benefit
Hepatic
- Use with caution and reduce dose if needed
Contraindicated
- Patient at risk for CV ADR, acute glaucoma
- Caution in diabetes
Smoking
- May need to adjust dose if patient stops during treatment
Anipsychotic - Aripiprazole
- Type of antipsychotic
- Contraindications and cautions
Second generation antipsychotic
- Partial DA and 5HT agonist
Elderly
- May still be effected by EPSE and anticholinergic effects
- Start low and go slow
Children
- High risk of metabolic and hypoprolactinaemia which may disturb growth/maturation
Pregnancy
- Always consider risk/benefit
- Consider infant withdrawal
Hepatic
- Low dose in impairment
Contraindicated
- Along side used with strong CYP3A4 or 2D6 inhibitors
Choice of antipsychotics in schizophrenia
- Commence with oral second generation
- Depend on patient presentation, clinical experience, properties of drug and anticipated tolerability
Clozapine is most effective but has many serious side effects (older drug)
- Known to cause agranulosytosis and requires frequent monitoring (narrow therapeutic window)
Key interventions to consider in schizophrenia
- One antipsychotic at a time
- Use for adequate duration before changing
- Individualized treatment
- Use non pharm therapies (counseling, behavior therapy, psychosocial therapy)
- Manage comorbidities
- Maintain physical health
Comorbidity of schizophrenia
Mental
- Depression
- Anxiety
- Substance abuse
- Suicidality
Physical
- CVD
- Obesity
- Diabetes
- Respiratory
Lifestyle
- Smoking
- High alcohol intake
- Poor diet and physical care
- Lack of exercise
