Psychopharmacology Flashcards
Antidepressant efficacy is similar so what is selection based on?
Past history of a response, side effect profile and coexisting medical conditions.
There is a delay typically of 2-4 weeks after a therapeutic dose is achieved before symptoms improve.
If no improvement is seen after a trial of adequate length (at least 2 months) and adequate dose, either switch to another antidepressant or augment with another agent.
What are indications for antidepressant use?
Unipolar and bipolar depression, organic mood disorders, schizoaffective disorder, anxiety disorders including OCD, panic, social phobia, PTSD
(premenstrual dysphoric disorder and impulsivity associated with personality disorders)
What are the classifications of antidepressants?
Tricyclics (TCAs)
Monoamine Oxidase Inhibitors (MAOIs)
Selective Serotonin Reuptake Inhibitors (SSRIs)
Serotonin/Noradrenaline Reuptake Inhibitors (SNRIs)
How do SSRIs work and what are the side effects?
Block the presynaptic serotonin reuptake
Treat both anxiety and depressive sx
Most common side effects include GI upset, sexual dysfunction (30%+!), anxiety, restlessness, nervousness, insomnia, fatigue or sedation, dizziness
Very little risk of cardiotoxicity in overdose
Can you develop a discontinuation syndrome with SSRIs?
Yes, Can develop a discontinuation syndrome with agitation, nausea, disequilibrium and dysphoria
More common with shorter half life drugs so conisder switching to fluoxetine.
What is activation syndrome with SSRIs?
Activation Syndrome: Cause increased serotonin. Can be distressing for patient.
Nausea, increased anxiety, panic and agitation.
Typically last 2 – 10 days
Fluoxetine (Prozac): what are some pros and cons of this medication?
Pros
- Long half-life so decreased incidence of discontinuation syndromes. Good for pts with medication noncompliance issues
- Secondary to long half life, can give one 20mg tab to taper someone off SSRI when trying to prevent SSRI Discontinuation Syndrome
Cons
- Long half life and active metabolite 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 pts already on a number of meds
SERTRALINE: What are the pros and cons of this SSRI?
Pros
- Very weak P450 interactions (only slight CYP2D6)
- Short half life with lower build-up of metabolites
- Less sedating when compared to paroxetine
Cons
- Max absorption requires a full stomach
- Increased number of GI adverse drug reactions
What are the disadvantages of TCAs side effect profile?
Very effective but potentially unacceptable side effect profile i.e. antihistaminic (sedative effects), anticholinergic, antiadrenergic
Lethal in overdose (even a one week supply can be lethal!)
Can cause QT lengthening even at a therapeutic serum level
What are MAOIs very effective and what are their side effects?
Bind irreversibly to monoamine oxidase thereby preventing inactivation of amines such as norepinephrine, dopamine and serotonin leading to increased synaptic levels
Are very effective for resistant depression
Side effects include orthostatic hypotension, weight gain, dry mouth, sedation, sexual dysfunction and sleep disturbance
Hypertensive crisis can develop when MAOI’s are taken with tyramine-rich foods or sympathomimetics. *Cheese Reaction!!
What is Serotonin syndrome and how can it be avoided?
Serotonin Syndrome can develop if take MAOI with meds that increase serotonin or have sympathomimetic actions.
Serotonin syndrome sx include abdominal pain, diarrhea, sweats, tachycardia, HTN, myoclonus, irritability, delirium. Can lead to hyperpyrexia, cardiovascular shock and death.
To avoid 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.
How do SNRIs work and what are they used for?
Inhibit both serotonin and noradrenergic reuptake like the TCAS but without the antihistamine, antiadrenergic or anticholinergic side effects
Used for depression, anxiety and possibly neuropathic pain
E.g. Duloxetine, Venlafaxine, Vortioxetine
What is an example of a novel antidepressant?
Mirtazapine
Different mechanism of action may provide a good augmentation strategy to SSRIs. Is a 5HT2 and 5HT3 receptor antagonist
Can be utilised as a hypnotic at lower doses secondary to antihistaminic effects
Very sedating at lower doses
What are examples of SSRIs?
Citalopram, Fluoxetine or Sertraline
What is the first line med for deppression?
SSRI
Less desirable choices include Paroxetine and Mirtazapine because of sedation and wt gain.
Not a dual reuptake inhibitors if treatment niave.
Not a TCA because of side effects
How is treatment resistance managed?
Combination of antidepressants eg SSRI or SNRI with Mirtazepine
Adjunctive treatment with Lithium
Adjunctive treatment with atypical antipsychotic eg Quetipaine, Olanzapine or Aripiprazole
ECT!!
When should prophylaxis be used in the context of antidepressants?
First episode continue for 6mth to a year
Second episode continue for 2 years
Third episode discuss life long
When are mood stabilisers indicated?
Bipolar, cyclothymia, schizoaffective
Classes: Lithium, anticonvulsants, antipsychotics
What factors predict positive response to lithium?
Prior long-term response or family member with good response
Classic pure mania
Mania is followed by depression
What is done before starting lithium and how is it monitored?
Before starting :Get baseline U&E and TSH. In women check a pregnancy test- during the first trimester is associated with Ebstein’s anomaly
Monitoring: Steady state achieved after 5 days- check 12 hours after last dose. Once stable check level 3 months and TSH and creatinine 6 months.
Goal: blood level between 0.6-1.2
What are the side effects of lithium?
Most common are GI distress including reduced appetite, nausea/vomiting, diarrhoea
Thyroid abnormalities
Nonsignificant leukocytosis
Polyuria/polydypsia secondary to ADH antagonism. In a small number of patients can cause interstitial renal fibrosis.
Hair loss, acne
Reduces seizure threshold, cognitive slowing, intention tremor
What are the signs of mild, moderate & severe lithium toxicity?
Mild- levels 1.5-2.0 see vomiting, diarrhea, ataxia, dizziness, slurred speech, nystagmus.
Moderate-2.0-2.5 nausea, vomiting, anorexia, blurred vision, clonic limb movements, convulsions, delirium, syncope
Severe- >2.5 generalized convulsions, oliguria and renal failure
What factors predict a positive response to Valproic acid (Depakote)?
Valproic acid is as effective as Lithium in mania prophylaxis but is not as effective in depression prophylaxis.
Factors predicting a positive response:
- rapid cycling patients (females>males)
- comorbid substance issues
- mixed patients
- Patients with comorbid anxiety disorders
Better tolerated than Lithium
How is Valproic acid given and who should it be avoided in?
Before start: Baseline LFTs, preg test & FBC
Monitoring: steady state achiever after 4-5 days-check 12 hrs after last dose & repeat CBC and LFTs
Goal: Target level is between 50-125
AVOID in women of child bearing age due to NTD
What are the side effects of valproic acid?
Thrombocytopenia and platelet dysfunction
Nausea, vomiting, weight gain
Sedation, tremor
Hair loss
What is the first line agent for acute mania and mania prophylaxis?
CARBAMAZAPINE (Tegretol)
Indicated for rapid cyclers and mixed patients
How is Carbamazepine dosing monitored?
Before: baseline LFTs, FBC and an ECG
Monitoring: Steady state achieved after 5 days -check 12 hours after last dose and repeat CBC and LFTs
Goal: Target levels 4-12mcg/ml
Need to check level and adjust dosing after around a month because induces own metabolism.
How is Carbamazepine dosing monitored?
Before: baseline LFTs, FBC and an ECG
Monitoring: Steady state achieved after 5 days -check 12 hours after last dose and repeat CBC and LFTs
Goal: Target levels 4-12mcg/ml
Need to check level and adjust dosing after around a month because induces own metabolism.
What are the side effects of carbamazepine?
- Rash (most common)
Nausea, vomiting, diarrhea
Sedation, dizziness, ataxia, confusion
AV conduction delays
Aplastic anemia and agranulocytosis
Water retention due to vasopressin-like effect which can result in hyponatremia
Drug-drug interactions!
Lamotrigine (Lamictal) has indications similar to other anticonvulsants: What is it also used for and how is it given?
Before: Baseline LFTs
Titrate up slowly as faster titration has a higher incidence of a serious rash
If patient stops med for 5 days have to start dosing regime again
What are the side effects of Lamotrigine>
Nausea/vomiting
Sedation, dizziness, ataxia and confusion
The most severe are toxic epidermal necrolysis and Stevens Johnson’s Syndrome. The character/severity of the rash is not a good predictor of severity of reaction. Therefore, if ANY rash develops, discontinue use immediately.
Drugs that increase lamotrigine levels: VPA (doubles concentration, so use slower dose titration), sertraline.
Why if any rash appears while using Lamotrigine should you stop using the medication immediately?
The most severe are toxic epidermal necrolysis and Stevens Johnson’s Syndrome.
The character/severity of the rash is not a good predictor of severity of reaction. Therefore, if ANY rash develops, discontinue use immediately.
What is the first line for pure mania?
LITHIUM
What is a rapid cycler defined as?
4 or more depressive or manic episodes/year
What should be done if a patient on a anticonvulsant has an increase in their LFTs?
It is not unusual for patients on anticonvulsants to experience an increase in LFTs and as long as they do not more than triple no change in therapy is indicated.
Continue to monitor over time
What are the indications for the use of antipsychotics?
Schizophrenia, schizoaffective disorder, bipolar disorder- for mood stabilization and/or when psychotic features are present, psychotic depression, augmenting agent in treatment resistant anxiety disorders.
What can dopamine hypoactivity cause?
Dopamine suppresses acetylcholine activity.
Dopamine hypoactivity can cause Parkinsonian movements i.e. rigidity, bradykinesia, tremors), akathisia and dystonia.
(dopamine release inhibits/regulates prolactin release. Blocking dopamine in this pathway will predispose your patient to hyperprolactinemia (gynecomastia/galactorrhoea/decreased libido/menstrual dysfunction))
What are examples of typical antipsychotics and how do they work?
Are 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. Examples include Fluphenazine, Haloperidol, Pimozide.
How do atypical antipsychotics work?
The Atypical Antipsychotics - atypical agents are serotonin-dopamine 2 antagonists (SDAs)
They are considered atypical in the way they affect dopamine and serotonin neurotransmission in the four key dopamine pathways in the brain.
What are examples of atypical antipsychotics?
RISPERIDONE
- Increased extrapyramidal side effects (dose dependent)
- Most likely atypical to induce hyperprolactinemia
- Weight gain and sedation (dosage dependent)
OLANZAPINE
- Weight gain
- May cause hypertriglyceridemia, hypercholesterolemia, hyperglycemia (even without weight gain)
QUETIAPINE
- Abnormal LFTs
- OH
ARIPRAZOLE
- Low EPS, no QT prolongation, low sedation
- Probably first line due to its low sedation and not being associated with weight gain
What is the most likely atypical to cause HYPERPROLACTINAEMIA?
RISPERIDONE
What atypical antipsychotic is reserved for treatment resistant patients and what side effects does it have?
CLOZAPINE
- Agranulocytosis
- 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
Why do people with psychotic illnesses relapse?
Commonest psychotic symptom is lack of insight
People with psychotic illnesses relapse most commonly due to non compliance
Only 30% of patients take medication as prescribed
What is there a clear link to after a third episode of schizophrenia?
Clear link to reduced functioning, lower IQ and negative symptoms.
Consider Long Acting Intramuscular!!
What are the adverse effects of antipsychotics?
Tardive Dyskinesia (TD)-involuntary muscle movements that may not resolve with drug discontinuation
Neuroleptic Malignant Syndrome (NMS): Characterized 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
What agents can be used for EPS?
Anticholinergics such as benztropine, trihexyphenidyl, diphenhydramine
Dopamine facilitators such as Amantadine
Beta-blockers such as propranolol
Need to watch for anticholinergic SE particularly if taken with other meds with anticholinergic activity ie TCAs
Many atypical antipsychotics can cause dyslipidemia, abnormal LFT’s and elevated blood sugars and there is a class risk of diabetes unrelated to weight gain so you need what?
Fasting lipid profile
Fasting blood sugar
LFTs
CBC
What is Akathisia not uncommon with?
RISPERIDONE
(Need to treat akathisia because it is associated with an increased risk for suicide- use propranolol or anticholinergic agent)
What are anxiolytics used to treat?
Many diagnoses including panic disorder, generalized Anxiety disorder, substance-related disorders and their withdrawal, insomnias and parasomnias.
In anxiety disorders often use anxiolytics in combination with SSRIS or SNRIs for treatment.
Buspirone: What are the pros and cons?
Pros:
- Good augmentation strategy- Mechanism of action is 5HT1A agonist. It works independent of endogenous release of serotonin.
- No sedation
Cons:
- 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.
What are benzodiazepines used to treat and what are the side effects?
Used to treat insomnia, parasomnias and anxiety disorders.
Often used for CNS depressant withdrawal protocols ex. ETOH withdrawal.
Side effects/cons:
Somnolence
Cognitive deficits
Amnesia
Disinhibition
Tolerance
Dependence
