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 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.
