Mental health pharmacology Flashcards

1
Q

Typical antipsychotics

A
  • Mechanism of action: Dopamine D2 receptor antagonists blocking dopaminergic transmission in the mesolimbic pathways
  • Adverse effects: Extrapyramidal side-effects and hyperprolactinaemia common
  • Examples: Haloperidol, Chlopromazine
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2
Q

Atypical antipsychotics

A
  • Mechanism of action: acts on a variety of receptors (D2, D3, D4, 5-HT)
  • Adverse effects: extra-pyramidal side effects and hyperprolactinaemia less common, metabolic effects
  • Weight gain, clozapine is associated with agranulocytosis and hyperprolactinaemia
  • Examples: Clozapine, Risperidone, Olanzapine
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3
Q

Anti-psychotics: Extra pyramidal side effects

A
  • Parkinsonism: instead change to an alternative (quetiapine/olanzapine) or prescribe anticholingeric medication
  • Acute dystonia: sustained muscle contraction i.e. torticollis, oculogyric crisis. May be managed with procyclidine
  • Akathsia (severe restlessness)
  • Tardive dyskinesia (late onset of choreoathetoid movements, abnormal, involuntary. May occur in 40% of patients, may be irreversible. Most common is chewing and pouting of jaw

Specific risks in the elderly: increased risk of stroke, venous thromboembolism

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4
Q

Other side effects of antipsychotics

A
  • antimuscarinic: dry mouth, blurred vision, urinary retention, constipation
  • sedation, weight gain
  • raised prolactin= may result in galactorrhoea, due to inhibition of the dopaminergic tuberoinfundibular pathway
  • impaired glucose tolerance
  • neuroleptic malignant syndrome: pyrexia, muscle stiffness
  • reduced seizure threshold (greater with atypicals)
  • prolonged QT interval (particularly haloperidol)
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5
Q

Adverse effects of clozapine

A
  • agranulocytosis (1%), neutropaenia (3%)
  • reduced seizure threshold - can induce seizures in up to 3% of patients
  • constipation
  • myocarditis: a baseline ECG should be taken before starting treatment
  • hypersalivation
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6
Q

Antipsychotics: monitoring

A
  • FBC, U&E, LFT= at start of therapy, annually. Clozapine requires more frequent monitoring of FBC (initially weekly)
  • Lipids, weight= at the start of therapy, at 3 months, annually
  • Fasting blood glucose, prolacting= at start of therapy, at 6 months, annually
  • Blood pressure: baseline, frequently during dose titration
  • ECG: baseline
  • Cardiovascular risk assessment: annually
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7
Q

Key points about treating depression

A
  • Treat single episode for 6-9 months after remission
  • Risk of relapse is high and increases with each episode
  • Long term treatment for multiple episodes
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8
Q

SSRI discontinuation symptoms

A
  • Dizziness, light headedness, vertigo, ataxia
  • Nausea, vomiting, diarrhoea
  • Lethargy, headache, tremor, sweating, anorexia
  • Paraesthesia, numbness, ‘electric shock’ like sensation
  • Irritability, anxiety, agitation, low mood
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9
Q

Smoking and psychotropic drugs

A
  • 7-12 cigarettes a day is sufficient for maximum induction of CYP1A2
  • In smokers the clozapine metabolism is increased reducing clozapine plasma levels
  • Smokers require higher doses of clozapine to achieve same plasma levels
  • On stopping smoking you should reduce the clozapine dose gradually
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10
Q

Antipsychotics and physical health

A

Long term risks: Cardiovascular, Dyslipidaemia, Weight gain, Diabetes, Hyperprolactinaemia, EPSE

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11
Q

QTc and antipsychotics

A
  • Dose dependent
  • May present as: increased QT interval, torsades de pointes, ventricular fibrillation, sudden death
  • Normal QTc= Women <470ms, Men <440ms
  • A QT prolonged to 450ms is of some concern. >500ms can lead to torsades de points and requires prompt review and action
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12
Q

Dyslipidaemia and anti-psychotics

A

Olanzapine and clozapine associated with the greatest risks. Discuss dietary and lifestyle on initiation/ early in treatment. Full lipid profile at baseline, 3 months and annually. If QRISK above 10% prescribe a Statin.

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13
Q

Antipsychotics and Hyperprolactinaemia

A
  • Dopamine antagonists increase prolactin levels, can be caused by all antipsychotics
  • Less risk= Clozapine, olanzapine, quetiapine and ariprazole
  • Symptoms include: galactorrhoea, amenorrhoea, gynaecomastia, hypogonadism, sexual dysfunction
  • Linked with osteoporosis and breast cancer
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14
Q

Depot antipsychotics and general side effects

A

1st generation antipsychotics tend to cause movement disorders whilst 2nd generation cause more metabolic disturbance

Depot antipsychotics
* Long acting formulation, only some anti-psychotics available
* Can be given 1-4 weekly, monthly and 3 monthly
* Advantages: useful in non-compliant patients, useful if struggle to take oral
* Disadvantages: plasma level maintained for long time (ADR, interactions), unable to switch antipsychotics quickly

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15
Q

Neuromalignant syndrome

A
  • Body temperature rises rapidly and it can be fatal in 1-3 days
  • Symptoms: Fever, Diaphoresis (sweating), rigidity, confusion, fluctuating consciousness, fluctuating BP, tachycardia, elevated creatine kinase, altered LFT
  • More common in first generation but second generation antipsychotics can also cause, as well as antidepressants (SSRI, lithium)
  • Combination of antipsychotic and SSRI increases risk
  • Risk factors: drug increase or reduction, abrupt withdrawal of anticholingeric, psychosis, organic brain disease, alcoholism, parkinsons, if agitated and in need of restraint/seclusion
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16
Q

Diagnosing and treating Neuroepileptic malignant syndrome

A
  • Diagnostic test: no specific test, CK >1000, AST/ALT
  • Withdraw antipsychotics, lithium, antidepressant for at least 5 days. Begin with small dose and increase slowly
  • Monitor temp, pulse, BP
  • Use benzodiazepine- im lorazepam
  • Correct any dehydration and hyperpyrexia
  • In hospital: rehydration, Bromocriptine and dantrolene (muscle relaxant)
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17
Q

Lithium

A
  • Class of drug: mood stabiliser, anti-manic drugs
  • Mechanism of action: mimics sodium, modulates dopaminergic and serotonergic transmission
  • Licensed indications: acute manic or hypomanic episodes, adjunct in treatment resistant depression, prophylaxis bipolar affective disorder. Control of aggressive behaviour or intentional self harm
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18
Q

Antipsychotics: management of sexual side effects

A
  • Switch to low risk antidepressant= mirtazapine, vortioxetine, agomelatine
  • Dose reduction
  • In men sildenafil/tadalafil help
  • Other medication: Buspropion, transdermal testosterone
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19
Q

Antidepressant induced hyponatraemia

A
  • Onset within 30 days of starting treatment
  • Not usually dose related, most likely SIADH
  • Serotonergic drugs more likely (SSRI/SNRI) but can be caused by all antidepressants
  • Monitor Na at baseline, 2, 4 weeks and then 3 monthly for those at high risk
  • If Na >125mmol/L monitor Na daily until normal, consider withdrawing antidepressant.
  • May need to withdraw NSAID, diuretic. Start antidepressant from another class
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20
Q

Antipsychotics and antidepressants: hepatic and renal impairement

A

SSRI’s have a bleeding risk which is increased with antiplatelet/NSAIDs

Antipsychotics and antidepressants: hepatic and renal impairment
* Antipsychotics renal: avoid sulpride and amisulpride and highly anticholingeric agents. Use first gen (haloperidol) and second gen (olanzapine)
* Antidepressants renal: sertraline and citalopram
* Antipsychotic hepatic: Sulpride/amisulpride, Paliperidone
* Antidepressant hepatic: Sertraline or mirtazapine

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21
Q

Depression and psychological therapies

A
  • Step 1
  • Step 2: Low intensity psychological intervention (Individual guided self help based on principles of CBT or Computerised CBT (CCBT)), Group CBT
  • Step 3: High intensity psychological interventions; CBT, Interpersonal therapy (IPT), Behavioural activation, Behavioural couples therapy
  • Step 4: High intensity psychological intervention (as above but possibly delivered in inpatient setting)
22
Q

Social anxiety, OCD and body dysmorphic psychological therapies

A

Social anxiety psychological therapies
* Adults: individual CBT. If rejected can offer short term psychodynamic psychotherapy
* Children: individual or group CBT, consider involving parents or care givers

Obsessive compulsive disorder and body dysmorphic disorder treatment: CBT (including exposure response prevention

23
Q

PTSD: psychological therapies

A
  • Adult: trauma focussed CBT, Eye movement desensitisation and reprocessing (EMDR)
  • Children and young people: An individual trauma focussed CBT intervention. Consider EMDR if CBT not helpful and from 3 months after trauma
24
Q

Psychological therapy for psychosis and schizophrenia in adults

A

Family intervention, individual CBT for psychosis/schizophrenia

25
Q

CBT

A
  • General concept is that our thoughts, emotions, physiological sensations and behaviours are interconnected and trap us in a vicious cycle
  • Tends to focus on current events and not historic
  • Identifies situations/triggers that cause distress
26
Q

Interpersonal therapy

A
  • Used to treat acute depression (rather than chronic depression)
  • Aims to: Reduce the symptoms of depression, Improve social adjustment and interpersonal functioning.
  • IPT has a distinct focus on; conflict with another person, life changes, grief and loss, difficulties in starting or keeping a relationship going.
27
Q

Eye movement Desensitisation and Reprocessing (EMDR)

A
  • Intended to help people recover from distressing events e.g. flashbacks, intrusive images/thoughts, depression and anxiety.
  • Aims to desensitise the person to the emotional impact of the memory (so that they can think about it without experiencing such strong emotions).
  • Person has to recall the traumatic event while they also move their eyes from side-to-side, hear a sound in each ear alternately, or feel a tap on each hand alternately. This helps the brain reprocess the information more like an ordinary memory, reducing its intensity.
28
Q

Family intervention is a psychological therapy that should

A
  • include the person with psychosis or schizophrenia if practical
  • be carried out for between 3 months and 1 year
    include at least 10 planned sessions
  • take account of the relationship between the main carer and the person with psychosis or schizophrenia
  • have a specific supportive, educational or treatment function and include negotiated problem solving or crisis management work.
29
Q

Short term psychodynamic psycotherapy

A

Focuses on different forces in the patients life that may be causing difficulties, which may have begun in childhood. It should include discussion about social anxiety, a focus on any relationships linked to the person’s social anxiety and exploring any feelings of shame. The therapist should encourage the person to confront any social situations they are anxious about and help them improve their social skills.

30
Q

Different types of therapy

A
  • Cognitive Analytic Therapy (CAT)= Integrates cognitive and analytical approaches. Looks at relationships/roles.
  • Dialectical Behavioural Therapy (DBT)= Targets those with emotional regulation difficulties/personality difficulties
  • Radically Open DBT (RO-DBT)= Targets those experiencing excessive self control, often referred to as overcontrol (OC).
  • Compassion Focussed Therapy (CFT)= Targets those with high shame/self-criticism.
31
Q

Referral for psychological therapy

A
  • Don’t immediately refer for specialist services, may not be the right time. Start with support and psychoeducation moving on to guided self help and psychological well being interventions like relaxation
  • May use an integrative approach for complex patients
  • Patients needs to be willing to make change
  • Contraindications= normal response to life event (grief), vague problems, difficulty focusing, unwilling to undertake talking therapy
32
Q

Tricyclic antidepressants (TCA’s)

A
  • e.g. amitriptyline, lofepramine, clomipramine
  • Inhibit 5-HT and NA uptake which Produces therapeutic effect
  • Block of M1, H1, 1 receptors produces side effects= causes sedation, postural hypotension and anticholingeric side effects (dry mouth, constipation, urinary retention, blurred vison)
  • Poorly tolerated and toxic in overdose
  • In depression Lofepramine is second line, Clomipramine second line for OCD
33
Q

Selective serotonin reuptake inhibitors (SSRI’s)

A
  • For example: fluoxetine, paroxetine, sertraline, citalopram
  • Inhibits 5-HT uptake: produces therapeutic benefit against depression, OCD, panic, anxiety
  • Side effects: nausea, early increased anxiety, sexual dysfunction
  • Well tolerated and good first line treatment
34
Q

Serotonin and Noradrenaline Reuptake inhibitors (SNRI’s)

A
  • e.g. venlafaxine, duloxetine
  • Inhibit 5-HT and NA uptake: Produces therapeutic effect, Produces side effects similar to SSRI
  • Better tolerated than TCAs and probably more effective than SSRIs for severe depression therefore good second/third line treatment
35
Q

Noradrenaline and Serotonin Selective Antagonist (NaSSA)

A
  • e.g. mirtazepine
  • Blocks alpha2 receptors= Produces antidepressant effect (Increases 5-HT release)
  • Blocks 5-HT2 receptors= Produces decreased anxiety
  • Blocks H1 receptors= Produces sedation
  • Blocks 5-HT2 and H1= Produces weight gain
  • Possibly more potent than SSRIs plus lacks sexual side effects. Can cause marked weight gain. Used second line
36
Q

5- HT2 antagonist

A

I.e. Trazodone
- Similar potency to other antidepressants but often added to SSRI’s or SNRI’s at low doses to provide sedation
- Rare side effect of priapism

37
Q

Monamine Oxidase inhibitors

A
  • Traditional e.g. phenelzine, tranylcypromine
  • Food & drug interaction: builds up tyramine, cheese, wine, chocolate
  • RIMA (sub class) e.g. moclobemide
  • Increase levels of 5-HT, NA (and dopamine - traditionals)
  • Third/fourth line treatments for severe and/or atypical depression
38
Q

Agomelatine

A
  • Melatonin MT1 and MT2 agonist + 5-HT2C antagonist
  • Extremely well tolerated – but LFT checks needed (hepatotoxicity rare)
  • Rarely used. Option when tolerability a major issue
39
Q

Ketamine (IV/oral) and esketamine (intranasal)

A
  • Dissociative anaesthetic (used at sub-anaesthetic dose)
  • Glutamate NMDA receptor antagonists
  • Uniquely rapidly acting (within hours)
  • Can acutely reduce suicidality
  • VERY expensive
40
Q

NICE: antidepressants

A
  • SSRI first line: If not effective – an alternate SSRI.
  • Reasonable alternatives = mirtazepine, but consider moclobemide, reboxetine, lofepramine. Venlafaxine or an older TCA for severe depression
  • Vortioxetine as third line agent
  • Esketamine for treatment resistant depression (Decision pending)
41
Q

TCA’s: contraindications and cautions

A
  • Contraindications: Manic phase of bipolar disorder; arrhythmias; heart block; immediate recovery period after myocardial infarction
  • Cautions: Bipolar, Psychosis, CVD, epilepsy, epilepsy, diabetes, hyperthyroidism,
42
Q

SSRI’s: contraindications and cautions

A
  • Contraindications: poorly controlled epilepsy, mania
  • Cautions: bleeding disorders, pre-existing raised QTc (citalopram and escitalopram), diabetes
43
Q

SNRI’s and NaSSA contraindications and cautions

A

SNRIs
- Contraindications: High risk of arrythmia, uncontrolled hypertension
- Cautions: Bleeding disorders, epilepsy, bipolar, glaucoma, diabetes

NaSSA= Cautions: CVD, bipolar, epilepsy, psychosis, prostatism, diabetes

44
Q

When to prescribe antidepressants

A
  • Antidepressants are a first line treatment for: moderate and severe MDD in adults, Sub-threshold depression that has persisted for 2 years or more.
  • Antidepressants are an option for mild MDD especially if: there is a history of moderate to severe recurrent depression. The depression has persisted for more than 2–3 months
  • Antidepressants are not a first line treatment for short duration sub-threshold depression in adults but consider if: there is a prior history of moderate to severe recurrent depression. The depression persists for more than 2–3 months
45
Q

Antidepressants: assessing response

A
  • Review response after 4-6 weeks
  • After 2-4 weeks there should be at least some response; 4-6 weeks there should be significant response
  • Assess for response, partial response and no response
  • If partial response increase dose, if no response switch drug
  • Treat for 6-12 months from remission, if risk factors longer
  • If multiple risk factors review annually
46
Q

Managing difficult to treat depression

A

Augment if partial response and switching failed previously
- First line: Lithium, quetiapine, aripiprazole
- Second line: Mirtazepine (with SSRIs or SNRIs), T4, risperidone
- Others: pramipexole, stimulants, esketamine, oestrogen, testosterone, etc etc

47
Q

Depression: Additional therapeutic interventions

A
  • Psychotherapies (+/- medication)
  • Neurostimulation (ECT, tDCS, TMS, VNS)
  • Psychosocial (behavioural activation, community reconnection)
  • Self management (e.g. on-line)
48
Q

Hypnotics and anxiolytics

A
  • Hypnotics: Benzodiazepines, Z-drugs
  • Anxiolytics: Benzodiazepine, Buspirone, Gabapentinoids

Hypnotics and Anxiolytics both increase GABA transmission causing: Anxiolysis, Sedation, Muscle relaxation, Anticonvulsant, Amnesia, Reduction of alcohol withdrawal symptoms.

49
Q

Gabapentinoids

A
  • Pregabalin (licensed for GAD), gabapentin
  • Act by enhancing GABA function through an effect on ion channels,
  • Effective for GAD, including at high doses for difficult to treat anxiety
  • Also can help neuropathic pain
  • Side effects: drowsiness, fatigue, ataxia, blurred vision, diplopia, dizziness, constipation
  • Avoid in patient with history of alcohol or substance misuse
  • Been reclassified as controlled drugs
50
Q

Other drugs used to manage anxiety or hypnosis

A
  • Any drug that has anti-histamine properties E.g. anti-histamines, TCAs, antipsychotics
  • 5-HT2 antagonists= Trazadone, Mirtazepine, second generation antipsychotics
  • NB – the first line pharmacological treatments for anxiety disorders are SSRIs