Pharmacological + non-pharmacological management of mental health conditions

Question 1

What is the principle of action of anti-depressants?

Answer 1

Monoamine hypothesis: enhance activity of monoamine neurotransmitter (NA + 5-HT)

Question 2

When are antidepressants indicated in depression and what do you do if its not working?

Answer 2

• indicated for moderate-severe depression a/w psychomotor/physiological changes
• most take 2-3w to work and up to 6w for main effect to be seen. first few weeks may have agitation/anxiety/suicidal ideation
• if no effect at a typical dose then switch the drug, if partial benefit then increase the dose

1st line - SSRI
2nd line - another SSRI/mirtazapine
Specialists: venlafaxine, lofepramine (TCA), augmentation with lithium/antipsychotics

Question 3

How long should you use an antidepressant for?

Answer 3

• at least 6m from remission in depression/12m in GAD

* in recurrent depression maintain for at least 2y

Question 4

Discontinuation syndrome

Answer 4

Stopping AD may cause this - best to reduce dose slowly esp for venlafaxine which has a short half life

Causes sweating, shakes, agitation, insomnia, headache, irritability, N+V, paraesthesia, clonus

Question 5

Serotonin syndrome

Answer 5

Uncommon ADR due to excessive serotonergic activity

A/w SSRIs (esp fluoxetine-long half life), SNRI, MAOI, and interactions with other meds like opioids, TCAs, anticonvulsants, lithium, OTC meds, antiemetics – check individual interactions

CF: headache, agitation, hypomania, confusion, coma, autonomic sx (shiver, sweat, hyperthermia, tachycardia, nausea, diarrhoea), somatic sx (myoclonus, clonus, hyperreflexia, tremor)

M: stop drug, fluids, monitor

Question 6

SSRIs mechanism + side effects

Answer 6

Selective serotonin reuptake inhibitors - increase serotonin activity

Used in depression + anxiety disorders

S/e: GI (nausea, dyspepsia, bloating, diarrhoea/constipation), STRESS (Sweating, Tremor, Rash, Extrapyramidal se(rare), Sexual dysfunction, Somnolence, Stopping (discontinuation syndrome))

Question 7

Examples of SSRIs

Answer 7

E.g. sertraline (50-200mg, safest in heart disease), citalopram (20-40mg, risk of QTc prolongation), escitalopram (10-20mg, also QTc), fluoxetine (20-60mg, risk of serotonin syndrome when switch, longest half life), paroxetine (20-60mg, risk of discontinuation syndrome)

Question 8

SNRIs

Answer 8

Serotonin + noradrenaline reuptake inhibitors - also bind to NA reuptake receptors so NA + serotonin retained at nerve junction - more rapid effects than SSRIs so good for 2nd line treatment and sometimes in neuropathic pain

E.g. duloxetine, venlafaxine

S/e similar to SSRI, more chance of dry mouth, headache, dizzy, nausea, HTN (monitor BP at higher doses) + sexual dysfunction

Question 9

NARI - selective noradrenaline reuptake inhibitor

Answer 9

V specific inhibitor e.g. reboxitine

Similar s/e profile. Avoid abrupt withdrawal. Cautions in many conditions.

Question 10

Mirtazapine

Answer 10

Recommended after 2 SSRIs not worked or if a prominent feature is not eating/not sleeping, is a unique class with serotonin + histamine activity, some NA activity and an alpha blocker (so increases appetite)

S/e: sedation, weight gain, dry mouth, postural hypotension, oedema, tremor, dizziness, confusion, abnormal dreams, myalgia

Question 11

Tricyclic antidepressants

Answer 11

Used to be used for depression but not much now cos of s/e, often used at low doses for neuropathic pain or migraine prophylaxis

Inhibits reuptake of NA + serotonin, and binds to cholinergic receptors

E.g. amitriptyline, clomipramine, dosulepin, imipramine, lofepramine

Some have sedative properties. Variety of S/e. CI in recent MI/heart block/mania.

Question 12

Side effects of TCAs

Answer 12

• anticholinergic: blurred vision, urinary retention, dry mouth, constipation
• CVS: long QT, postural hypotension, tachycardia, syncope
• Hypersensitivity: urticaria, photosensitivity
• Psychiatric: mania, confusion, delirium, drowsiness
• Metabolic: weight gain (increased appetite)
• Endocrine: testicular enlargement, gynaecomastia, galactorrhoea
• Neuro: convulsions, dyskinesias, dysarthria, paraesthesia, taste disturbance, tinnitus, headache, tremor

Question 13

Signs of TCA toxicity

Answer 13

Pyrexia
Blurred vision
Pupil dilation (mydriasis)
Confusion
Seizures
Tachycardias
Cardiac arrest

M: activated charcoal (within 1h), sodium bicarbonate (if wide QRS), BZD for seizures

Question 14

MAOIs

Answer 14

Monoamine uptake inhibitors - prevent breakdown of dopamine, NA + 5HT

Not used much now and only be specialists as dangerous interactions. E.g. moclobamide, tranylcypromine

• SE: postural hypotension, arrhythmias, drowsy, insomnia, headache, weight gain, hepatic derangement
• Hypertensive reactions with tyramine - must avoid cheese/pickled meats/wine/alcoholic or low alcohol drinks
• Interactions: opiates, insulin, SSRIs, TCAs, anti-epileptics
• Toxic in OD

Question 15

Vortioxetine

Answer 15

Newer drug for difficult to treat cognitive sx

Well-tolerated, may cause mild nausea

Question 16

How do antipsychotics work?

Answer 16

• anti-dopaminergic: all work on D2/3 receptors, typical AP usually have higher affinity
• serotonergic: mostly atypicals, this improves affective + negative sx but causes metabolic s/e
• anti-histaminergic, anti-adrenergic, anti-cholinergic - cause many s/e

Question 17

What are the types of side effects of antipsychotics?

Answer 17

• Extrapyramidal s/e (esp typical)
• Anti-muscarinic (esp atypical): can’t see (blurred vision), can’t pee, can’t shit, can’t spit
• Anti-histaminergic: sedation, weight gain
• Anti-adrenergic: postural hypotension, tachycardia, ejaculatory failure
• Endocrine: hyperprolactinaemia (esp typical cos of dopamine inhibition so prolactin secretion less inhibited), can cause reduced BMD/menstrual disturbance/galactorrhoea
• Metabolic (Esp atypical): impaired glucose tolerance, hypercholesterolaemia
• Cardiac: QTc prolongation (esp haloperidol)
• Clozapine: hypersalivation, agranulocytosis
• Neuroleptic malignant syndrome: rare, life threatening reaction

Question 18

Extrapyramidal side effects

Answer 18

• Parkinsonism (w-m): bradykinesia, rigidity, coarse tremor, expressionless face, shuffling gait
• Akathisia (first few months, reduce dose + propranolol): unpleasant restlessness
• Dystonia (days): acute painful muscle spasms in neck/jaw/eyes-oculogyric crisis
• Tardive dyskinesia (years, may be irreversible): choreoathetoid movements usually of jaw

Treatment usually antimuscarinics e.g. procylidine. Tardive dyskinesia doesn’t respond to this and may be worsened

Question 19

Neuroleptic malignant syndrome

Answer 19

Rare, life-threatening reaction to AP in first 10d after treatment beginning/dose increase

CF: pyrexia, confusion, muscle rigidity, sweating, autonomic instability (tachycardia, fluctuating BP), delirium, rhabdomyolysis, renal failure, PE, seizures

RF: high potency dopamine antagonists (typical LPs) in antipsychotic-naiive pt, high doses, young men

M: stop drug, fluid resuscitation, reduce temp, consider BZD, consider dantrolene (muscle relaxant)

Question 20

What monitoring is required for pt on antipsychotics?

Answer 20

• FBC, U+E, LFTs: initiation then annually (amisulpiride doesnt need LFT)
• Clozapine - FBC weekly for 18w, then fortnightly for 1y, then monthly
• Fasting blood glucose: baseline, at 4-6m then yearly (olanzapine + clozapine need it every 4-6m)
• Lipids: baseline, 3m, yearly
• Prolactin: baseline, 6m, yearly
• ECG: may need before initiating
• BP: before + frequently during (amisulpiride, aripiprazole don’t affect BP)
• Weight

Question 21

What route may antipsychotics be given?

Answer 21

• Oral usually
• Short-acitng IM
• Depot injections (long acting) every 1-4w e.g. flupentixol, risperidone, olanzapine. Bypass 1st pass metabolism + increase adherence

Question 22

Typical antipsychotics

Answer 22

Haloperidol, flupentixol, zuclopenthixol, chlorpromazine, sulpiride

More likely to cause EPSEs, raised prolactin, dizziness, sexual dysfunction

Question 23

Atypical antipsychotics

Answer 23

More serotonergic activity + specific dopamine blockage. 1st line for schizophrenia

Olanzapine, risperidone, quetiapine, amisulpiride, aripiprazole (fewer S/e), cloazpine

S/e: metabolic syndrome (esp clozapine + olanzapine), higher risk of stroke + VTE

Question 24

Clozapine

Answer 24

Most efficacious atypical AP. Used in schizophrenia after 2 APs have failed

Oral suspension

S/e:

• common: anorexia, constipation, hyper salivation, malaise, speech disorders, urinary incontinence, metabolic syndrome
• uncommon: agranulocytosis (1%)
• rare: GI hypo motility, myocarditis, pancreatitis

Titrate dose slowly + monitor for autonomic dysregulation. Alter dose if smoking starts/stops

Question 25

Antipyschotic OD

Answer 25

Coma, seizure, arrhythmia, hypotension

Question 26

Beta blockers

Answer 26

Reduce ANS activation - biopsycho feedback - reduce somatic sx like palpitations/tachycardia/tremor Usually propranolol CI in asthma, COPD, heart block, acute LVF

Question 27

Benzodiazepines

Answer 27

Bind to GABA receptors to potentiate the effect (positive allosteric modulators) - reduce neurone excitability Ind: insomnia, anxiety disorders severe, delirium tremens, alcohol detoxification (chlordiazepoxide), acute psychosis, violent behaviour --> all short term use (also seizures obv ) Types: * long acting: diazepam, chlordiazepoxide, clonazepam * short acting: lorazepam, temazepam, midazolam S/e: drowsy, dizzy, confusion, ataxia, amnesia, dependence, paradoxical increase in aggression, muscle weakness, resp depression Toxicity: ataxia, dysarthria, nystagmus, coma, respiratory depression --> IV flumazenil if indicated (don't always need to give it) Withdrawal syndrome: up to 3w after stopping long acting/within a day from short-acting. Tremor, anxiety, sweating, convulsion, perceptual disturbance, irritable, insomnia, reduced appetite, tinnitus

Question 28

Pregabalin

Answer 28

Increases GABA in brain so reduces neurone activity Used in anxiety (?), neuropathic pain, epilepsy. Meant to be short-term but often used for longer, less dependence/tolerance than BZD but still misused S/e are sedation + weight gain

Question 29

Z-drugs

Answer 29

Anxiolytic used to induce sleep short-term, not a BZD Zopiclone, zolpidem, zaleplon

Question 30

Lithium carbonate mechanism

Answer 30

Effective but mechanism unknown! Used for BPAD + schizoaffective disorder, significant evidence that it reduces self harm/suicide . Can be used in acute episodes or for maintenance Teratogenic - Ebstein's anomaly CI in renal failure, pregnancy, breastfeeding, untreated hypothyroidism

Question 31

Side effects of lithium treatment

Answer 31

``` Diarrhoea Impaired renal function Diabetes insipidus Fine tremor Hypothyroidism Weight gain Oedema Metallic taste Leucocytosis Idiopathic intracranial hypertension ```

Question 32

Lithium toxicity

Answer 32

Levels 1.5-2mM: N+V, coarse tremor, ataxia, muscle weakness, apathy Severe >2mM: nystagmus, dysarthria, hyperreflexia, oliguria, hypotension, convulsions, coma M: stop lithium, high fluids with NaCl to stimulate osmotic diuresis, may need dialysis

Question 33

What monitoring is needed for lithium therapy?

Answer 33

Has a narrow therapeutic window so need monitoring: * pre-treatment: U+E, TFT, ECG, pregnancy test * 6 monthly: U+E (renal impairment usually irreversible) * 12 monthly: TFT (hypothyroidism-usually reversible) * Lithium levels: weekly when starting/changing dose (12h post-dose) until stable, then 3m. Dehydration + interactions (NSAIDs, TD, ACEi) cause toxicity

Question 34

Sodium valproate

Answer 34

Anti-convulsant can be used as a mood stabiliser if lithium + atypical AP not working Avoid in women of child bearing age - causes neural tube defects S/e: GI, weight gain, aggression, LFT derangement, thrombocytopenia, peripheral oedema, ataxia, tremor, fatigue, teratogenic

Question 35

Carbamazepine

Answer 35

An anticonvulsant can be used after 1st line tx for mania or for alcohol withdrawal s/e: drowsy, leukopenia, diplopia, blurred vision, rash, thrombocytopenia potent enzyme inducer

Question 36

Lamotrigine

Answer 36

An anticonvulsant that can be used in BPAD, good in women of child bearing age as can't have SV. but doesnt prevent/treat manic episodes so only used for the depressive episodes s/e: GI, rash, headache, tremor. potential for Stevens-Johnson syndrome

Question 37

What drug types can be used as mood stabilisers?

Answer 37

* lithium * anticonvulsants * atypical antipsychotics - rapid onset so good for acute mania, e.g. quetiapine (less chance for interacting with lithium for toxicity)

Question 38

Cholinesterase inhibitors

Answer 38

* Donepezil, galantamine, rivastigmine * inhibit breakdown of ACh in brain ( AD a/w lower cholinergic acitivity) * for mild-mod AD to improve cognitive sx + neuropsychiatric sx like apathy * s/e: N/V/D, insomnia, muscle cramps, anorexia, bradycardia. EPSE (rivastigmine) * monitoring: pulse regularly, ECG at initiation * CI in heart disease + epilepsy * cautioned in asthma/COPD, PUD, arrhythmias

Question 39

Memantine

Answer 39

Glutamine (NMDA) receptor antagonist which lowers neuronal excitability Ind: mod-severe AD, or if cholinesterase inhibitors CI Used for agitation/challenging behaviour

Question 40

What drugs are used for ADHD?

Answer 40

* Methylphenidate or dextroamphetamine: CNS stimulant so potential for misuse. Can cause growth failure, CI in suicidal ideation * Atomoxetine: NA reuptake inhibitor. Can cause suicidal ideation

Question 41

Electroconvulsive therapy

Answer 41

Small current passed through brain to induce modified epileptic seizure - use GA + muscle relaxant to limit motor effects Usually need 6-12 sessions, 2x a week Indicated in prolong/severe mania, catatonia or severe depression (treatment resistant, suicidal ideation/serius risk to others, not eating drinking) S/e: peripheral nerve palsies, arrhythmias, confusion, risks of GA, myalgia, headaches, short term memory impairment, status epilepticus, amnesia, death CI: recent MI, unstable #, RICP, cerebral aneurysm, recent stroke, h/o status epilepticus, severe GA risk

Question 42

Cognitive behavioural therapy

Answer 42

Active treatment self help/group/individually Need pt motivation Aims to help people identify + challenge automatic negative thoughts + modify abnormal underlying core beliefs

Question 43

Psychodynamic psychotherapy

Answer 43

Individual, couple or group Intense. Explore unconscious by free association, therapist interprets this, client develops insight to change maladaptive behaviours

Question 44

Family therapy

Answer 44

 Family members seen together  Focuses on the family system and its ability to help family problems + individual mental illness  Aims to correct impaired communication and dysfunctional communication

Question 45

Counselling

Answer 45

Form of relieving distress by active dialogue with the aim to help client find solution to problems. Indicated in adjustment disorder, mild depression, normal and pathological grief, adverse life events, substance misuse, chronic medical conditions, prior to decision-making e.g. genetic counselling.

Question 46

Behavioural therapies

Answer 46

Based on learning theory, esp operant conditioning (behaviour is reinforced if it has positive consequences for the individual and prevents negative consequences). E.g. relaxation training (stress and anxiety), systemic desensitisation (gradual exposure-phobias), flooding (rapid exposure – not commonly used), exposure and response prevention (repeatedly exposed to situation causing anxiety but prevented from doing the compulsive actions - OCD and phobias), behavioural activation (making realistic plans to carry out activities then gradually increasing this – depressive disorders).

Question 47

Psychoeducation

Answer 47

Deliver information to help understand and cope with their illness. Name and nature, likely causes, what health services can do to help, what they can do to help themselves.

Question 48

Supportive psychotherapy

Answer 48

Psychological support given by mental health professionals to people with chronic and disabling mental illness. Aims to help people cope with adversity/unsolved problems, includes active listening, reassurance, explaining illness, providing guidance and possible solutions and allowing patient to express themselves in a safe environment.

Question 49

Interpersonal therapy

Answer 49

Depression and ED. Focus on interpersonal problem e.g. bereavement, relationship issues or loss, interpersonal deficit – which may be causing difficulties in initiating or maintaining relationships.

Question 50

Eye movement desensitisation + reprocesing

Answer 50

Helps patients access and process traumatic memories – for PTSD. Recall emotionally traumatic material while focusing on an external stimulus (e.g. following finger). Possibly placebo…

Question 51

Dialectical behavioural therapy

Answer 51

Used for borderline PD. Uses CBT and group skills training to provide alternative coping strategies to self-harm when faced with emotional instability.

Question 52

Cognitive analytic therapy

Answer 52

Cognitive therapies + psychoanalytic approaches. Analysing problems, how they began and how they affect every day life + reasons behind symptoms.

Question 53

What is transference?

Answer 53

- Transference: patient re-experiences strong emotions from earlier events – positive transference when emotions are positive and vv for negative - Counter-transference – therapist affected by powerful emotions felt by patient during therapy and reflects what patient is feeling