Psychopharmacology Flashcards
what are the indications for use of antidepressant medication?
- Unipolar and bipolar depression
- organic mood disorders
- schizoaffective disorder
- anxiety disorders including OCD, panic, social phobia, PTSD
- premenstrual dysphoric disorder
- impulsivity associated with personality disorders
list the different classes of antidepressant drugs
- SSRIs
- Tricyclics (TCAs)
- Monoamine Oxidase Inhibitors (MAOIs)
- Serotonin/noradrenaline reuptake inhibitors (SNRIs)
- novel antidepressants
SSRIs side effects
Most common:
- GI upset
- sexual dysfunction (30%+)
- anxiety
- restlessness
- nervousness
- insomnia
- fatigue or sedation
- dizziness
Very little risk of cardiotoxicity in overdose.
Can develop a discontinuation syndrome with agitation, nausea, disequilibrium and dysphoria.
what causes activation syndrome?
related to SSRIs
- caused by increased seretonin. Can be distressing for patient.
- nausea, increased anxiety, panic and agitation.
- typically last 2-10 days so warn patients!
Fluoxetine (Prozac) Pros
- long half-life so decreased incidence of discontinuation syndromes. Good for patients with medication noncompliance issues.
- initially activating so may provide increased energy.
- secondary to long half-life, can give one 20mg tab to taper someone off SSRI when trying to prevent SSRI discontinuation syndrome.
Fluoxetine (Prozac) Cons
- long half-life and active metabolites may build up (e.g. not a good choice in patients with hepatic illness)
- significant P450 interactions so this may not be a good choice in patients already on number of meds.
- initial activation may increase anxiety and insomnia.
- more likely to induce mania than some of the other SSRIs.
Sertraline Pros
- very weak P450 interactions (only slightly CYP2D6)
- short half-life with lower build up of metabolites.
- less sedating when compared to paroxetine.
Sertraline Cons
- max absorption requires a full stomach
- increased number of GI adverse drug reactions.
TCAs Cons
- very affective drugs but potentially unacceptable side effect profile i.e. antihistaminic, anticholinergic, antiadrenergic.
- lethal in overdose (even a one week supply can be lethal)
- can cause QT lengthening even at therapeutic serum level.
- secondary TCAs have same side effects as tertiary TCAs but are generally less severe.
tertiary TCAs examples
Imipramine
Amitryptyline
Doxepin
Clomipramine
secondary TCAs examples
desipramine
nortriptyline
how do Monoamine Oxidase Inhibitors (MAOIs) work as antidepressants?
- bind irreversibly to MAO thereby preventing inactivation of amines such as norepinephrine, dopamine and serotonin leading to increased synaptic levels.
- very effective for resistant depression.
MAOIs side effects
- orthostatic hypotension
- weight gain
- dry mouth
- sedation
- sexual dysfunction
- sleep disturbance
Hypertensive crisis can develop when MAOI’s are taken with…
tyramine-rich foods (such as cheese) or sympathomimetics (seretonin syndrome).
- To avoid seretonin syndrome need to wait 2 weeks before switching from an SSRI to an MAOI. The exception of fluoxetine where need to wait 5 weeks because of long half-life.
seretonin syndrome symptoms
- abdominal pain
- diarrhoea
- sweats
- tachycardia
- hypertension
- myoclonus
- irritability
- delirium
- can lead to hyperpyrexia, CV shock and death.
Venlafaxine (a SNRI) Pros
- minimal drug interactions and almost no P450 activity
- short half-life and fast renal clearance avoids build-up (good for geriatric populations)
Venlafaxine (a SNRI) Cons
- can cause 10-15 mmHG dose dependent increase in diastolic BP.
- may cause significant nausea, primarily with immediate-release (IR) tabs.
- can cause a bad discontinuation syndrome, and taper recommended after 2 weeks of administration.
- sexual side effects in > 30%.
Duloxetine (SNRI) Pros
- some data to suggest efficacy for physical symptoms of depression
- thus far less BP increase as compared to venlafaxine
Duloxetine (SNRI) Cons
- CYP2D6 and CYP1A2 inhibitor
- cannot break capsule, as active ingredient not stable within the stomach
- in pooled analysis had higher drop out rate
Novel antidepressant Mitrazapine Pros
- Different mechanism of action may provide a good augmentation strategy to SSRIs. Is a 5HT2 and 5HT3 receptor antagonist
- Can be utilized as a hypnotic at lower doses secondary to antihistaminic effects
Novel antidepressant Mitrazapine Cons
- Increases serum cholesterol by 20% in 15% of patients and triglycerides in 6% of patients
- Very sedating at lower doses. At doses 30mg and above it can become activating and require change of administration time to the morning.
- Associated with weight gain (particularly at doses below 45mg)
what are the management options for a patient with treatment resistance depression?
- combo of antidepressants e.g. SSRI or SNRI with Mirtazepine
- adjunctive treatment with lithium
- adjunctive treatment with atypical antipsychotic e.g. quetipaine, olanzapine or aripiprazole
- ECT
what are the management options for a patient with treatment resistance anxiety?
- high dose SSRI first
- combo of antidepressants e.g. SSRI or SNRI with Mitrazepine
- adjunctive treatment with atypical antipsychotic e.g. quetiapine, olanzapine or risperidone.
- adjunctive treatment with pregabalin or buspirone
- avoid diazepam
what are the indications for mood stabiliser drugs?
- bipolar
- cyclothymia
- schizoaffective disorder
what are the different classes of mood stabiliser drugs?
- lithium
- anticonvulsants
- antipsychotics
what is the only medication to reduce suicide rate?
lithium
factors prediciting positive response to lithium
- prior long-term response or family member with good response
- classic pure mania
- mania is followed by depression
what investigations should be performed before starting lithium?
- get baseline U&E and TSH
- pregnancy test in women
how is lithium monitored?
- steady state achieved after 5 days - check 12 hours after last dose. Once stable check level 3 months and TSH and creatinine at 6 months.
what is the goal level of lithium in bloods?
- 0.6-1.2
lithium side effects
- Most common > GI distress including reduced appetite, nause/vomiting and diarrhoea.
- thyroid abnormalities
- polyuria/polydypsia secondary to ADH antagonism. In a small no. patients can cause interstitial renal fibrosis leading to renal failure
- hair loss, acne
- reduces seizure threshold, cognitive slowing, intention tremor.
discuss mild, moderate and severe lithium toxicity symptoms
- Mild, levels 1.5-2: see vomiting, diarrhoea, ataxia, dizziness, slurred speech nystagmus.
- Moderate, 2-2.5: nausea, vomiting, anorexia, blurred vision, clonic limb movements, convulsions, delirium and syncope.
Severe, > 2.5: generalised convulsions, oliguria and renal failure
what tests must be taken before commencing treatment with Valproic acid?
- baseline LFTs
- pregnancy test
- FBC
why would you use valproic acid instead of lithium?
- Valproic acid is as effective as Lithium in mania prophylaxis but is not as effective in depression prophylaxis.
- Better tolerated than lithium.
Valproic acid side-effects
- CI in women of child bearing age as increased risk of neural tube defects secondary to reduction in folic acid.
- thrombocytopenia and platelet dysfunction
- nausea, vomiting, weight gain
- sedation, tremor
- hair loss.
when is Carbamazepine (Tegretol) indicated?
- first-line agent for acute mania and mania prohylaxis
- indicated for rapid cyclers and mixed patients
what tests must be performed before commencing carbamazepine treatment?
baseline LFTs
FBC
ECG
carbamazepine side effects
- rash, most common SE seen
- nasuea, vomiting, diarrhoea
- sedation, dizziness, ataxia, confusion
- AV conduction delays
- aplastic anemia and agranulocytosis (< 0.002%)
- water retention due to vasopressin-like effect which can result in hyponatraemia
- drug-drug interactions
when is Lamotrigine indiacted (Lamictal)?
indications similar to other anticonvulsants
also used for neuropathic/chronic pain
Lamotrigine side effects
- nausea/vomting
- sedation, dizziness, ataxia and confusion.
- most severe: TENS and Steven Johnson’s syndrome, if ANY rash devlops, discontinue use immediatly.
- valproic acid and sertraline increase lamotrigine levels.
Antipsychotics indications for use
- schizophrenia
- schizoaffective disorder
- bipolar disorder for mood stabilisation and/or when psychotic features are present
- psychotic depression
- augmenting agent in treatment resistant anxiety disorders
what dopamine pathway is responsible for positive symptoms (hallucinations, delusions and thought disorders)?
Mesolimbic: projects from the dopaminergic cell bodies in the ventral tegmentum to the limbic system.
In a psychotic patient, there is too much dopamine.
Which dopamine pathway is considered to be where negative symptoms and cognitive disorders (lack of executive function) arise?
Mesocortical: projects from the ventral tegmentum (brain stem) to the cerebral cortex.
Problem here for a psychotic patient, is too little dopamine.
Which dopamine pathway is involved in movement regulation?
Nigrostriatal: projects from the dopaminergic cell bodies in the substantia nigra to the basal ganglia.
- remember that dopamine suppressed ACh activity.
- dopamine hypoactivity can cause Parkinsonian movements, akathisia and dystonia.
blocking dopamine in which pathway will predispose your patient to hyperprolactinemia?
Tuberoinfundibular: projects from the hypothalamus to the anterior pituitary.
- dopamine release inhibits/regulates prolactin release.
what is a typical antipsychotic?
give examples of high and low potency ones
- D2 dopamine receptor antagonists.
- high potency typical antipsychotics bind to the D2 receptor with high affinity. As a result, they have higher risk of extrapyramidal side effects.
- e.g. Fluphenazine, Haloperidol, Pimozide.
- low potency typical antipsychotics have less affinity for D2 receptor but tend to interact with nondopaminergic receptors > cardiotoxic, anticholinergic adverse effects (sedation, hypotension)
- e.g. chlorpromazine and thioridazine
antipsychotic adverse affects
- Tardive Dyskinesia (TD) - involuntary muscle movements that may not resolve with drug discontinuation - risk approx. 5% per year.
- Neuroleptic Malignant Syndrome (NMS): characterised by severe muscle rigidity, fever, altered mental status, autonomic instability, elevated WBC, CPK and LFTs. Potentially fatal.
- Extrapyramidal side effects (EPS): acute dystonia, Parkinson syndrome
- Akathisia be aware increased risk of suicide
what are atypical antipsychotics?
- seretonin-dopamine 2 antagonists (SDAs)
- less propensity for EPS
- atypical in the way they affect dopamine and seretonin neurotransmission in the four keu dopamine pathways in the brain.
risperidone side effects
increased extrapyramidal side effects (dose-dependent)
- most liekly atypical to induce hyperprolactinemia
- weight gain and sedation (dosage dependent)
olanzapine side-effects
- weight gain
- may cause hypertriglyceridemia, hypercholesterolemia, hyperglycemia (even without weight gain)
- may cause hyperprolactinemia (< risperidone)
- may cause abnormal LFTs
Quetiapine side effects
- May cause abnormal LFT’s
- May be associated with weight gain, though less than seen with olanzapine
- May cause hypertriglyceridemia, hypercholesterolemia, hyperglycemia (even without weight gain), however less than olanzapine
- Most likely to cause orthostatic hypotension
how is schizophrenia classified as treatment-resistant? how is it managed?
- poor response to 2 first-line antipsychotics at adequate dose for 8 weeks
- clozapine used in this case
why is clozapine reserved for treatment-resistant patients?
- Is reserved for treatment resistant patients because of side effect profile but this stuff works!
- Associated with agranulocytosis (0.5-2%) and therefore requires weekly blood draws x 6 months, then Q- 2weeks x 6 months)
- Increased risk of seizures (especially if lithium is also on board)
- Associated with the most sedation, weight gain and abnormal LFT’s
- Increased risk of hypertriglyceridemia, hypercholesterolemia, hyperglycemia, including nonketotic hyperosmolar coma and death with and/or without weight gain
How is akathisia, a side-effect of antipsychotics treated?
inability to remain physically still
propanolol or diazepam
Buspirone (Buspar) Pros
an anxiolytic
- good augmentation strategy in anxiety - mechanism of action is 5HT1A agonist. It works independent of endogenous release of seretonin.
- no sedation.
Buspirone (Buspar) Cons
an anxiolytic
- takes around 2 weeks before patients notice results
- will not reduce anxiety in patients that are used to taking BZDs because there is no sedation effect to ‘take the edge off’.
Benzodiazepines side effects/cons
- somnolence
- cognitive deficits
- amnesia
- disinhibition
- tolerance
- dependence
