Therapeutics in mental health Flashcards
Mental illness causes:
- biological, genetic, physical, chemical
- social, psychological
4D’s +1
Significant Deviation from normal (“their normal” e.g. must include cultural features)
Patient has significant Dysfunction
Patient/others have significant Distress,
Patient presents a Danger to themselves or others… [Symptoms have been present for a significant Duration]
Therapeutics
- Environmental
Social services
Family - Psychological
General/supportive psychotherapy
Psychodynamic/interpretative psychotherapy
Interpersonal therapy
3. Behavioural Cognitive therapy Cognitive behavioural therapy Dialectic behavioural therapy Problem-solving therapy Meta-cognitive therapy
4. Physical
Psychotropic drugs
Electroconvulsive therapy
Transcranial methods
direct current stimulation
magnetic stimulation
Goals of psychopharmacology
Control immediate threat of harm to self and others Prevention of relapse - minimise - reduce suicidality Minimise symptoms - manage Minimise side effects - manage Improve quality of life - restore/improve functioning - improve social integration To integrate with other therapies contributing to the management of the patient with a mental health disorder
Main medication groups: 4A’s
Antidepressants
Anxiolytics
Mood stabilisers ́(“Antimanics”)
Antipsychotics
Collectively referred to as “psychotropics”
Side Effects of psychotropics
Dry mouth Constipation Nausea Sedation Insomnia Sexual dysfunction Tremor Weight gain
Depression
Cyclical & chronic disorder
Periods of illness separated by periods of good health
Onset: 20-40 years, Sx develop over time (days-weeks) Episode duration varies widely: 3-13 months
Most patients experience a 2nd episode (50-80%)
As patients get older, episodes last longer, have more Sx Over 20 year period – typically 5-6 episodes
Antidepressants primarily used for depressive symptoms of
1) Major depression
2) Depressed phase of bipolar disorder
The choice of antidepressant is determined by the following:
Anti-depressant adverse effect profile
Patients response or lack of response to previous treatment
Adverse effects of previous treatment
Family history of response to treatment
Risk of drug interaction with concurrently administered drugs
Antidepressant safety in overdose
Patient comorbidities
Finding Tx that ‘works’ can include lots of Tx trials, error, and juggling for any individual patient requiring pharmacological Tx
Tricyclic antidepressants (TCAs)
Heterogenous group, multiple pharmacological actions
• Tricyclic chemical structure à name
• Low therapeutic ratio, not 1st choice any longer
• Imipramine (earliest) has been around for 60+ years
ADRs
• Potentially lethal in overdose (seizures, arrhythmias)
• Similar receptor affinity profile as antipsychotics
- H1: Weight gain, drowsiness (can be ‘felt as sedation’)
- Alpha 1-adrenergic blockade: Postural hypotension
- Antimuscarinic: Blurred vision, dry mouth, urinary retention, constipation
- Sodium channel blockade: Arrhythmias, Seizures
• Hyponatraemia: SIADH (Syndrome of Inappropriate Antidiuretic Hormone)
Monoamine oxidase inhibitors (MAOIs)
Tranylcypromine & phenelzine
- Irreversible inhibitors – (up to 2 weeks)
- Non-selective – inhibit both A & B forms
- Interaction with dietary amines limits their use (!)
E.g. Tyramine, normally destroyed by GIT MAO-A
ADRs
Long lasting effects
Postural hypotension, dry mouth, blurred vision, urinary retention, weight gain, agitation, insomnia
Reversible inhibitors of MAO (RIMAs)
Moclobemide: Selective for MAO-A, reversible, dietary amines metabolised
- May lose selectivity at higher doses
ADRs
Transient… Postural hypotension, dry mouth, blurred vision, urinary retention; Weight gain, agitation, insomnia
Serotonin & noradrenaline reuptake inhibitors (SNRIs)
Venlafaxine, Duloxetine
-“dual action antidepressant”
-Minimal dopamine, anticholinergic & antihistamine effects at standard doses
-May increase BP
-Considered even more toxic in overdose than TCAs –
high risk of arrhythmia
NRIs – noradrenaline reuptake inhibitors:
• Reboxetine
SSRI ADRs
Irritability, agitation, anxiety, confusion, tremor ́Insomnia, disturbed sleep, sedation (yes!) ́Nausea, vomiting, GI upset, diarrhoea, anorexia ́Sexual dysfunction
Increased bleeding, vasodilation, hypertension ́ Headache
Dizziness
Hyponatraemia (10% of elderly patients affected)
-SIADH (Syndrome of Inappropriate Antidiuretic Hormone)
Serotonin syndrome
Noradrenergic & specific serotonergic antidepressants (NaSSA)
Mirtazapine
- Comparatively more sedation
- More weight gain
Antidepressant discontinuation
Withdrawal syndrome
́ sleep disturbances (insomnia, abnormal dreams)
́ GIT symptoms (N&V, diarrhoea, cramps)
́ ‘flu-like symptoms (lethargy, myalgia, chills)
́ agitation
́ disequilibrium (dizziness, vertigo, ataxia)
́ sensory disturbances (paraesthesias, electric shock)
Time frame
́ appear 1-3 days after cessation ́ last 7-14 days
Management:
́ taper doses, especially with short acting drugs – paroxetine
discontinuation syndrome
Clinical features: dizziness, anxiety, nausea, headache
Adverse effects: fatigue, diarrhoea, insomnia, tremor
Generalised Anxiety Disorder (GAD)
Onset gradual
Typical Sx include:
- Excessive anxiety for most days for at least 6 months
- Anxiety is not restricted to specific situations (is “general”)
- Palpitations, sweating, trembling, dry mouth, SOB, uncomfortable feeling in chest/abdomen, derealisation, chills
One other psychiatric symptom in 62% e.g. depression ́
EtOH dependence common (self medication)
High level of non-pharmacological Tx
-E.g. Psychotherapy, CBT, relaxation
Panic attacks can also occur in several anxiety disorders
Medications - anxiety
Sedative/hypnotics, benzodiazepines
- Potentiate GABA (Gamma Amino Butyric Acid)
- Bind to benzodiazepine GABAA receptor Antidepressants
- First line – SSRIs, SNRIs
- Second line – TCAs ́Mirtazapine ́MAOIs
- Partial 5HT1a agonist
Buspirone
Antipsychotics
b-blockers
Benzodiazepines (“benzos”)
Sedatives, hypnotics, provide rapid symptomatic relief from anxiety states
Examples include:
Diazepam, oxazepam, alprazolam, nitrazepam, temazepam, clonazepam, etc.
Lipid soluble drugs
Length of time in system greatly extended in
age due to lipophillic nature (liver metabolised)
Can lead to confusion, delirium, falls in elderly
Preference in elderly = use short acting drugs with no metabolites, e.g. oxazepam
For short-term use only
Benzos - tolerance, dependence, withdrawals
Tolerance
- Develops rapidly for hypnotic effects
- Takes longer to develop for anxiolytic effects
- Limited anxiolytic efficacy after 4 months (or less)
Dependence
-Physical (4weeks of daily use may be all that is required!)
Repeated withdrawals from BZEs can increase severity of withdrawal symptoms
Withdrawal Sx
-Agitation, hostility, dysphoria, insomnia, sweating, tachycardia, tremors, muscular tension, derealisation, depersonalisation
At worst
-Psychosis (hallucinations), seizures, increased sensitivity to excitatory amino acid neurotransmitter, glutamate
People taking Benzos - what to look out for on the ward
Memory impairment
Wakes up at night, “Forgot tablet” takes another! (at
home, or in rehab if they are self-medicating)
Daytime sleepiness
Respiratory depression
Other meds with synergistic effect
The elderly
More sensitive to SEs
Not eliminating as well, can accumulate BZEs, signs =
Dizziness, disorientation, vertigo, ↑ risk of falls (!)
More signs: Confusion, decreased reflexes, drowsiness, muscle weakness, shakiness, shortness of breath or trouble breathing, slow heartbeat, slurred speech, staggering, weakness
Psychosis
Symptom-based presentation, not a disease in itself ́ Characterised by a lost sense of reality
- Delusions: Fixed, false beliefs, E.g. grandiose (e.g. special powers), persecutory, etc.
- Hallucinations: False perceptions, Usually auditory, but can be tactile, olfactory, visual
Associated with schizophrenia, not exclusive to it
[Vs. Neurosis – associated with anxiety disorder (e.g.
obsession, phobic, compulsive) but intact reality sense]
Organic psychosis
Direct or indirect insult to brain, e.g. trauma, degenerative, infective, metabolic Functional psychosis Schizophrenic psychosis Affective psychosis Bipolar disorder Psychotic depression
Schizophrenia
It is a “split mind” (not split personality/dissociative disorder)
A major psychotic disorder with variable presenting profiles that reflects a disturbance of:
- Thought
- Perception
- Affect
- Behaviour
4A’s of schizophrenia
Loosened Association
Ambivalence
Autism
Loss of Affect
Sx of SZP often classified as:
Positive
- Reflects an addition to normal
behaviour… Delusions, Hallucinations, Disordered thought and speech
(This is what gets you into hospital)
Negative
- Reflects a subtraction of
behaviours… Blunted affect, Avolition, Alogia
(usually begins with these)
Antipsychotics
Two types: “Typical” and “Atypical”
Some prefer the terms 1st gen and 2nd gen
agents, i.e. FGA and SGA
Named ‘neuroleptics’ because they blocked motor activity and emotional expression
Efficacy dependent on D2 receptor antagonism
Antipsychotics: 2 typical ‘typicals’
Chlorpromazine - High sedation effect • Irritating to skin and oral mucosa • Phototoxic skin reactions • Original antipsychotic • Low potency antipsychotic – High doses required, lower incidence of EPSEs*, more likely to lower seizure threshold • D2 antagonist, muscarinic antagonist, H1 antagonist, alpha- 1 antagonist, sodium channel blocker
Haloperidol
- Classic D2 antagonist with minimal antimuscarinic and
antihistaminergic effects (also potent antiemetic)
- High potency antipsychotic
Low doses required
Associated with elongation of QT interval
High incidence of EPSE
Less likely to lower seizure threshold
Some alpha-1 antagonist activity
Depot injection available
The Atypicals (2nd gen antipsychotics)
Atypicals (not clozapine) are now 1st line therapy, based on SE profile rather than efficacy
Clozapine
- Effective against -ve symptoms
- Less extrapyramidal symptoms
- Being unlike any other antipsychotic, introduced ‘Atypicals’ (was a ‘prototype’)
- Efficacy dependent on combined D2 & 5HT2 receptor antagonism
- Introduced in 1960s, withdrawn due to high incidence of neutropenia (up to 3%) and agranulocytosis (up to 1%) !!!
- Reintroduced under strict haematological controls in late 1980s due to demonstrable improved efficacy over conventional antipsychotics
- Start low, go slow, monitor…
Others:
risperidone, olanzapine, amisulpride, quetiapine, aripriprazole
Clozapine - advantages
Advantages
- Most effective antipsychotic
- Reduces suicidality
- Improves most dimensions of SZP symptoms
- Very low incidence of EPSEs (has even been
used to manage EPSEs of other antipsychotics)
Clozapine - disadvantages
Disadvantages - Risk of neutropenia (agranulocytosis) - Regular blood monitoring - (WBCs) required - Risk of constipation - Myocarditis - Seizures - Weight gain - Metabolic disorder - Sialorrhoea (hypersalivation) - Drug interactions ́[S] for CYP1A2, 2D6, 3A4 *Most dangerous
Antipsychotics ADRS
Movement disorders (EPSE)
- dystonia
- akathisia
- Parkinsonism
Endocrine
- excess plasma prolactin - can lead to sexual dysfunction and osteoporosis
- SIADH
Syndromes (rare)
- serotonin
- neuroleptic malignant
Automatic Nervous system
- Antimuscarinic - dry mouth, urinary retention, blurred vision, tachycardia, constipation
- Alpha adrenergic receptor blockade
Metabolic
- hyperglycaemia (DM T1+2)
- dyslipidemia
- weight gain
Movement disorder effects:
Extrapyramidal Side Effects (EPSEs)
Dystonia
- Sustained muscle contraction causing twisting and abnormal postures
- Oculogyric crisis, cervical dystonia
- Caused by dopamine vs. acetylcholine imbalance in extrapyramidal system
- Treated with the antimuscarinic, benztropine
Pseudoparkinsonism
- Tremor, bradykinesia, rigidity
- Associated with gradual onset (over several weeks)
Akathisia
- Subjectively unpleasant state of motor restlessness
- Greater risk associated with
- High potency conventional antipsychotic (e.g. haloperidol)
Tardive Dyskinesia (“TDs)”
- (“Tardive”, i.e. late onset)
- Choreoathetoid movements
- Orofacial, fingers & toes, when severe can involve head, neck, trunk and hips
- Caused by striatal DA2 receptor super sensitivity
- Difficult to treat
What else do we use “Antipsychotics” for (e.g. in your ward) ?
́ Bipolar disorder as mood stabilisers, anxiety
́ OCD, e.g. as adjuncts to SSRIs
́ Augmentation in treatment-resistant depression
́ Tic disorders, e.g.. Tourette’s
́ Impulse control
́ Sedation
́ Pervasive development disorder, e.g. autistic spectrum disorder
́ Behavioural disturbance in dementia
́ Pain, e.g. quetiapine
́ Oncology, N&V
́ Illicit use
- Especially quetiapine, as an anxiolytic
- Used for managing the journey down
Bipolar affective disorder (manic depression)
Bipolar disorder is a mood disorder.
Intellectual and cognitive features remain intact
Social interaction depends on episode
Diagnostic feature is that episodes recur
Up to 90% of patients will experience depressive
episode
What is mania?
Required for diagnosis:
Abnormally expansive and elevated mood
Irritable mood, even hostile
Generally lasting > 6 days
- Can last weeks, even months, if untreated
- Can present with psychosis: (hallucinations, delusions)
- May require hospitalisation
Additionally, 3 or more of:
- Grandiosity, inflated self-esteem
Over-estimation of capabilities
Disinhibition, e.g. Financial (gambling), sexual
- Increased goal-directed activity
- Increased risk-taking
- Decreased sleep
- Distractible
- Pressurised speech, very talkative
- Flight of ideas, racing thoughts
The Mood Stabilisers (“Antimanics”)
Lithium
Anticonvulsants, e.g. valproate, carbamazepine Antipsychotics
Olanzapine, risperidone, quetiapine
Antidepressants often prescribed as adjuncts
- Care required due to risk of conversion to mania (!)
- Avoid in mania and mixed episodes (stop them!)
Sx may resolve in a few days
May take weeks to improve
Lithium (Li+)
Very effective for managing bipolar disorder
“Gold standard” (MOA still unknown)
Tolerance can develop
Intermittent Tx associated with worsening of natural course of bipolar illness
Protects against suicide
Li+ therapeutic index
Li+ has Low therapeutic index
Rapidly absorbed from GIT but long distribution phase
Therapeutic drug monitoring (TDM) required
- Sample best taken 12 h post dose
- Target serum levels = 0.6-1.0 mmol/L
- Monitor every 3-6 months
Pregnancy and lactation: Category D
- Associated with cardiac defects (!)
- Considered safe after week 26
- Avoid in breastfeeding, if possible
- Highly variable transfer to breast milk
- Otherwise close monitoring of infant required
- Benefits vs. risks
Li+ ADRs
Neurological
- Tiredness, drowsiness, muscle weakness, fatigue
- Tremor, ataxia, muscle twitching
- Tremor can be treated with propranolol ́
GIT
- Nausea, diarrhoea, anorexia
- Can occur at initiation, usually transient, can indicate toxicity
Renal
- Polyuria, mild thirst ́Nephrogenic diabetes insipidus
- Associated with chronic use
Thyroid
- Hypothyroidism
- Associated with chronic use
Overall Li+ ADRs
- Increase dramatically if serum levels > 1 mmol/L
- If serum > 2 mmol/L then associated with disorientation,
seizures, confusion, delirium
- Can progress to coma and death…
ADR mechanisms for Li+
Li+ inhibits adenylate cyclase, therefore …
Affects ADH (antidiuretic hormone) - Nephrogenic diabetes insipidus
Affects TSH (thyroid-stimulating hormone) - Hypothyroidism
Inhibits K channels on cardiac myocytes
- Arrhythmias, cardiac arrest due to impaired local K+ balance
Li+ = lots of significant Drug interactions
Diuretics
- Cause hyponatraemia, leading to renal system trying conserve it and therefore also conserving Li+ due to its similarity to Na+
NSAIDs
- Can increase serum Li by up to 40% ́PRN use of great concern
SSRIs/TCAs
- SIADH causes hyponatraemia (see above, re:
diuretics)
ACE-Is and ARBs
- Decrease Li+ excretion
Carbamazepine (structurally related to TCAs)
Prevention (of relapse) = part of Tx
Encourage (gently):
- Regularity of lifestyle
- Appropriate sleep pattern
- Adherence to medication (very challenging)
- Monitor impact of medication
- Avoid stresses and excesses
- Psychological education to detect signs of relapse
Antidepressant medication classes
- Tricyclics (TCAs)
- SSRIs (first line if pharmaco Tx indicated)
- Mirtazapine
- MAOI
Anxiolytics medication classes
Medications used for acute and chronic management
SSRIs – will also take time to work for this indication
- Anxiety can become worse before it gets better
- SSRIs are not ‘prn’
- Longer term Tx
Benzos (4th line ‘prn’ for GAD/panic disorder)
- If charted ‘prn’ don’t give regularly
Mood Stabilisers (“Antimanics”)
Acute management of manic episode
- Benzodiazepines, antipsychotics, lithium
SEs: lethargy, drowsiness
- Avoid alcohol
Chronic management of mood lability
- Lithium, Anticonvulsants
- Lethargy (commonly continues)
- Significant weight gain
- Monitoring
Antipsychotics - what to expect as a nurse
Typical and Atypical
- Eye contact may be lacking
- May appear not to be listening to you
- Take things slowly
- No assumptions
- Confirm indication (always! never assume)
- Have a carer?
- Or case worker?
- Explain to staff you may take a bit longer with this patient
Mental Health Medication Classes: Antipsychotic
Typical (First generation agents) and Atypical (Second generation agents)
Used to treat schizophrenia, mania, acute confusion
Mental Health Medication Classes: Antidepressants
Tricyclics SSRIs SNRIs NRI NAd and 5HT inhibitor MAOIs
Used to treat: Depression, pain and anxiety disorders (OCD, GAD, Phobia)
Mental Health Medication Classes: Mood stabilisers
Lithium
Anticonvulsants
Used to treat: Bipolar
Mental Health Medication Classes: anxiolytics (anti-anxiety)
Benzodiazepines (anxiety, alcohol withdrawal)
Beta blockers (somatic symptoms of anxiety)
Azapirone (anxiety)
