Which of the following drugs are classified as SSRIs?
Venlafaxine
Imipramine
Paroxetine
Bupropion
Phenylzine
Fluoxetine
Sertraline
Desvenlafaxine
Citalopram
Escitalopram
Which of the following drugs are classified as SNRIs?
Duloxetine
Mirtazapine
Selegiline
Which of the following drugs are classified as TCAs?
Trazodone
Amitriptyline
Clomipramine
Which of the following drugs are classified as MAO-Is?
Which of the following drugs are classified as Atypical?
Hypothesis Abnormally low levels of norepinephrine and/or underlie
Evidence for this hypothesis includes: Reserpine, an (old) antihypertensive drug depletes pre-synaptic stores of (NE) and is associated with depressive symptoms. Autopsy studies of the brains of depressed suicide victims indicate a level of NE and/or serotonin (5-HT) metabolism in most brain regions Drugs found to be beneficial act to enhance NE or 5-HT levels.
A major weakness to this hypothesis is the therapeutic lag – effects of drugs on NE or 5-HT levels are observed yet therapeutic benefit takes a minimum of 1 to 4 to occur
Hypothesis Depression is associated with elevated levels axis is dysregulated Abnormal (low) function is common in depression
Hypothesis Laboratory research indicates that antidepressants BDNF production in This requires term (weeks) not term (days) treatment BDNF increases neurogenesis and connectivity Stress, pain and depression can BDNF Imaging studies indicate reduced hippocampal volume (size) in
Which Serotonin Selective Reuptake Inhibitors (SSRIs) are approved for children?
Which Serotonin Selective Reuptake Inhibitors (SSRIs) are approved for adolescents?
Which of the following are uses for Serotonin Selective Reuptake Inhibitors (SSRIs)?
Depression
PTSD
Premature ejaculation
PMDD
Panic disorder
Bulimia
Menopausal “hot flashes”
Enuresis
OCD
GAD
Which of the following are true about SSRIs?
Rapid metabolism requires multiple doses per day
Risk of serotonin syndrome if switching to MAOI
Antagonist for 5-HT2A receptor
Mechanism of action: inhibition of serotonin transporter (SERT)
Some are potent inhibitors of CYP 2D6
Narrow therapeutic index
High selectivity for SERT (serotonin transporter)
Sedating - taken at bedtime
First line (with SNRIs) treatment for depression
High therapeutic index
Which seven of the following are the adverse effects of SSRIs?
Increased risk of bleeding by inhibiting SERT in platelets
Headaches, insomnia or hypersomnia
Significant weight gain in some patients
Increased sweating, urinary retention
Reduced sexual function; may improve over time on drug
Discontinuation syndrome (anxiety, irritability, confusion, crying)
Anticholinergic (muscarinic): dry mouth, constipation, urinary retention, blurred vision, confusion
Nausea, GI upset, diarrhea; all improve after the first week
Lowers seizure threshold, problem in epilepsy, alcoholism, eating disorders
Paroxetine is Category D – risk of heart defects with first trimester exposure
Which of the following are uses of Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs)?
Neuropathic pain
Vasomotor symptoms of menopause
Social anxiety
Sedation
Stress urinary incontinence
Which of the following are true about SNRIs?
Dominant class of antidepressants until ~ 1990s when SSRIs took over
Used for depression, neuropathic pain, GAD, stress urinary incontinence, vasomotor symptoms of menopause
Highly sedating and not associated with tolerance or dependence
Drugs have high selectivity for SERT and NET (norepinephrine transporter)
Has CNS stimulating effects, inhibits NE and dopamine transporters; increases presynaptic release of NE and dopamine
Venlafaxine is metabolized to desvenlafaxine by CYP 2D6
Narrow therapeutic index and bothersome side effects explain reduced use
Discontinuation symptoms with venlafaxine and desvenlafaxine are common
Used for depression, GAD, PTSD, OCD, panic disorder, PMDD, bulimia
Which of the following are the adverse effects of SNRIs?
Increased blood pressure and heart rate; not a problem in most patients
Which of the following are the uses for Tricyclic antidepressants (TCAs)?
Cardiac conduction delays; arrhythmogenic: Potentially lethal in overdose
Category D – risk of heart defects with first trimester exposure
Which of the following are true about TCAs?
Used in depression that is unresponsive to SSRIs and SNRIs
Drug-drug interactions with CNS depressants, e.g. antihistamines, alcohol, benzodiazepines
Potentially lethal in overdose
Less selectivity than SSRIs, SNRIs
As a class, they inhibit NET and SERT but variable profiles of individual drugs
Sedating – taken at bedtime
Metabolized by CYP 2D6, serum levels are affected by inhibitors
Efficacy is similar to SSRIs, SNRIs
Which of the following are the adverse effects of TCAs?
Sexual side effects
Histamine H1 antagonism: weight gain, sedation
Adrenergic α1 antagonism: orthostatic hypertension
Has been associated with priapism
Discontinuation syndrome (flu-like symptoms)
Which of the following are true about Trazodone?
Seldom used as monotherapy
Adjunct with SSRI for patients with insomnia
Used for depression and anxiety
Appetite stimulating – may be useful in depression plus anorexia
Not associated with sexual side effects, bleeding or weight gain
Is used as a hypnotic – highly sedating and not associated with tolerance or dependence
Which of the following are the adverse effects of Trazodone?
Potentially lethal in overdose (autonomic, cardiac, seizures)
Insomnia, restlessness
α1-antagonism: orthostatic hypotension
GI
Orthostatic hypotension
Anorexia
Which of the following are true about Bupropion?
Has CNS stimulating effects, inhibits NE and dopamine transporters
Not sedating
Irreversible inhibition of MAO-A and MAO-B; long duration of effect
Antagonist at adrenergic α2 and 5-HT2 receptor
Not used for anxiety
As effective as nicotine patches for smoking cessation
Increases presynaptic release of NE and dopamine
High selectivity for SERT
Which of the following are adverse effects of Bupropion?
Insomnia
Lowers seizure threshold
Agitation, anxiety, headache, nausea
Problem in epilepsy, alcoholism, eating disorders
Which of the following are true about Mirtazapine?
Sedating – useful for depression with insomnias
Drug-drug interactions with alcohol, benzodiazepines
Used in neuropathic pain, enuresis
H1 antagonist
Not associated with sexual side effects
Which of the following are adverse effects of Mirtazapine?
Dry mouth
Constipation
Weight gain
Which of the following are true about Monoamine oxidase inhibitors (MAOIs)?
Potential for drug/food interactions
MAO-B: metabolizes dopamine
MAO-B: metabolizes NE, 5-HT and dopamine
MAO-A: metabolizes NE, 5-HT and dopamine
Inhibits NE and dopamine transporters and increases presynaptic release of NE and dopamine
MAO-A: metabolizes dopamine
Used in treatment resistant depression
Which of the following are adverse effects of MOAIs?
Discontinuation syndrome
❌ ❌ ❌ (delirium), ❌ (hypertension, tachycardia, sweating) and ❌ (tremor), also ❌, shivering ❌ serotonergic ❌ at least ❌ before starting MAOI; ❌ requires 5 weeks Discontinue MAOI for 2 weeks ❌ starting a serotonergic agent Linezolid (antimicrobial), dextromethorphan, sumatriptan, tramadol, ❌, St. John’s wart can cause serotonin syndrome in the presence of ❌ or MAOI
Therapeutic use of antidepressants: ❌ Requires ❌ for benefit ❌ is ❌, if inadequate response then switch or ❌ another agent ~❌ respond to ❌ agent ~❌ respond if treatment is ❌ e.g. SSRI + bupropion/atypical antipsychotic Many patients continue ❌ doses for year
Therapeutic uses of ❌: Depression ❌ - SSRIs and SNRIs are approved for PTSD, OCD, social anxiety, GAD and panic disorder - Slower onset of benefit than ❌ ❌ - Effects on pain are ❌ of antidepressant effects - ❌, SNRIs are more effective than others ❌ - ❌ and sertraline are approved therapies ❌ - ❌ - As effective as nicotine patches ❌ - More success with ❌ than ❌ - ❌ stimulates appetite and used in anorexia ❌ - ❌ - Most antidepressants (except bupropion, ❌) have sexual side effects ❌ - SSRIs and SNRIs show benefit
Choosing an antidepressant At the population level, ❌ is ❌ for all drugs SSRIs and ❌ are first line therapies choice is often based on ❌, potential drug interactions, patient ❌ ❌
Antidepressants: Mechanisms of action ❌ (SSRIs) NET and SERT inhibition (❌, TCAs) 5-HT2C agonist (❌) α2 antagonist (❌) ❌ (mirtazapine) MAO inhibition (❌) ❌ (❌)
Adverse effects Mirtazapine has ❌ affinity for ❌ Antagonism of M, H1 and α1 is characteristic of ❌ - Dry mouth, sedation, ❌ - Cardiotoxicity ❌ - Weight gain, sexual dysfunction, drug interactions (plasma protein binding, drug metabolism), nausea, ❌
