What is the pharmacokinetic profile of Bupropion?
Rapidly absorbed, 85% protein binding, extensive hepatic metabolism, and biphasic elimination.
What is a key characteristic of Venlafaxine regarding CYP interactions?
It has fewer CYP interactions than SSRIs and is a substrate but NOT an inhibitor of CYP2D6 or other isoenzymes.
p.3
Pathophysiology of Depression
What is the effect of glucocorticoid receptors on BDNF synthesis?
Cortisol binding during chronic stress states decreases BDNF synthesis, leading to volume loss in stress-sensitive regions.
p.6
Adverse Effects and Drug Interactions
What significant warning is associated with Nefazodone?
Hepatotoxicity (FDA black-box warning).
p.6
Neurotransmitter Involvement in Depression
What receptors does Vortioxetine antagonize?
5-HT3, 5-HT7, 5-HT1D, and SERT.
p.10
Clinical Applications of Antidepressants
What is Desvenlafaxine investigated for?
Postherpetic neuralgia, chronic back pain, and Premenstrual Dysphoric Disorder.
p.7
Adverse Effects and Drug Interactions
What are the common adverse effects of Bupropion?
Agitation, insomnia, and anorexia.
p.11
Adverse Effects and Drug Interactions
What are the overdose effects of TCAs?
Lethal arrhythmias, blood pressure changes, and anticholinergic effects.
p.6
Adverse Effects and Drug Interactions
What are common adverse effects of antidepressants mentioned?
Sedation and gastrointestinal disturbances.
What interaction should be noted with Nefazodone and Triazolam?
Nefazodone increases triazolam levels; reduce triazolam dose by 75%.
p.9
Clinical Applications of Antidepressants
What are the analgesic properties of certain antidepressants?
They have NE and 5-HT reuptake blocking properties independent of mood effects.
p.3
Pathophysiology of Depression
How do sex steroids affect depression in post-partum and post-menopausal periods?
Decreased estrogen levels are associated with depression during these periods.
p.5
Clinical Applications of Antidepressants
What is the primary use of Tricyclic Antidepressants (TCAs)?
They are used primarily in depression unresponsive to more commonly used antidepressants like SSRIs and SNRIs.
p.5
Adverse Effects and Drug Interactions
What are common adverse effects of TCAs?
Anticholinergic effects such as dry mouth, constipation, urinary retention, blurred vision, and confusion.
p.9
Adverse Effects and Drug Interactions
What dietary recommendation is made for patients on MAOIs?
Low-tyramine diet, avoiding aged cheese, tap beer, soy products, and dried sausages.
p.1
Pathophysiology of Depression
What does the Neurotrophic Hypothesis suggest about depression?
Depression leads to loss of neurotrophic support, affecting neural plasticity and neurogenesis.
p.1
Pathophysiology of Depression
How do antidepressants affect neurogenesis?
Antidepressants increase neurogenesis and synaptic connectivity in cortical areas like the hippocampus.
p.10
Adverse Effects and Drug Interactions
What is a consideration for elderly patients when prescribing antidepressants?
They are sensitive to anticholinergic effects, particularly with TCAs.
p.5
Adverse Effects and Drug Interactions
What are the effects of Clomipramine?
It has high serotonergic activity and can lead to sexual side effects.
What serious drug interaction can occur with MAOIs?
Interaction with serotonergic agents leading to serotonergic syndrome.
p.10
Major Depressive Disorder (MDD) Characteristics
What are common mood and physical symptoms of Premenstrual Dysphoric Disorder?
Anxiety, depressed mood, irritability, insomnia, and fatigue.
p.10
Selective Serotonin Reuptake Inhibitors (SSRIs)
Which SSRIs are approved for treatment related to Premenstrual Dysphoric Disorder?
Fluoxetine and Sertraline.
p.1
Major Depressive Disorder (MDD) Characteristics
What is a key characteristic of Major Depressive Disorder (MDD)?
Depressed mood most of the time for at least 2 weeks or loss of interest or pleasure in most activities.
p.9
Adverse Effects and Drug Interactions
What somatic effects are associated with antidepressant agents?
Myoclonus, hyperreflexia, and tremor.
p.1
Clinical Applications of Antidepressants
What are some indications for antidepressants other than MDD?
Panic disorder, generalized anxiety disorder (GAD), PTSD, OCD, pain disorders, PMDD, vasomotor symptoms of menopause, and stress urinary incontinence.
What factors should be considered when choosing an antidepressant?
Cost, availability, adverse effects, potential drug interactions, patient history of response, and patient preference.
p.10
Adverse Effects and Drug Interactions
Which antidepressants have the least sexual side effects?
Bupropion, Mirtazapine, and Nefazodone.
p.1
Pathophysiology of Depression
What is the Monoamine Hypothesis in relation to depression?
It suggests a deficiency in the amount or function of serotonin, norepinephrine, and dopamine in the brain.
p.8
Adverse Effects and Drug Interactions
What syndrome can occur with the discontinuation of MAOIs?
Discontinuation syndrome, presenting with delirium-like symptoms.
p.7
Clinical Applications of Antidepressants
What is the primary use of Tetracyclic antidepressants?
For Major Depressive Disorder (MDD) unresponsive to other agents.
p.11
Clinical Applications of Antidepressants
What are TCAs and MAOIs used for in the treatment of MDD?
They are used as 2nd or 3rd line treatment.
How does Vilazodone function pharmacodynamically?
It is a potent SERT inhibitor and a partial 5-HT1A receptor agonist.
p.11
Adverse Effects and Drug Interactions
What FDA warning is associated with all antidepressants?
Increased suicidality in patients under 25 years old.
p.6
Selective Serotonin Reuptake Inhibitors (SSRIs)
What is the primary action of Trazodone?
Weak, selective SERT inhibitor.
p.3
Adverse Effects and Drug Interactions
What are common adverse effects of SSRIs?
Common adverse effects include nausea, gastrointestinal upset, decreased libido, headache, and weight gain.
p.11
Adverse Effects and Drug Interactions
What is a notable interaction concern with MAOIs?
They have the most serious drug interactions among antidepressants.
p.3
Selective Serotonin Reuptake Inhibitors (SSRIs)
How do SSRIs inhibit serotonin transporter (SERT)?
SSRIs inhibit SERT through allosteric inhibition, leading to increased serotonin levels in the synaptic cleft.
p.1
Neurotransmitter Involvement in Depression
What is the relationship between tryptophan and serotonin synthesis?
Tryptophan is a precursor for serotonin synthesis; diets low in tryptophan can lead to relapse in depressed patients.
p.9
Clinical Applications of Antidepressants
What is a significant risk for bipolar patients when using antidepressants?
Switching to mania or more rapid cycling.
What are the primary metabolites of Nefazodone?
Hydroxynefazodone and m-cpp.
p.10
Clinical Applications of Antidepressants
What is the role of Bupropion in smoking cessation?
It decreases the urge to smoke, mood symptoms, and weight gain during nicotine withdrawal.
p.4
Adverse Effects and Drug Interactions
Which antidepressants inhibit CYP2D6 and can increase the concentration of its substrates?
Paroxetine and Fluoxetine.
p.11
Adverse Effects and Drug Interactions
What treatment is recommended for TCA overdose?
Cardiac monitoring, airway support, gastric lavage, and sodium bicarbonate.
p.11
Adverse Effects and Drug Interactions
What are common overdose effects of MAOIs?
Autonomic instability, hyperadrenergic symptoms, confusion, delirium, fever, and seizures.
p.8
Adverse Effects and Drug Interactions
Why are MAOIs rarely used?
Due to toxicity and potentially lethal food and drug interactions.
p.2
Pathophysiology of Depression
What abnormalities are associated with the neuroendocrine hypothesis of depression?
Abnormalities in the HPA axis and elevated cortisol levels.
What is the primary substrate for MAO-A?
Norepinephrine (NE), Epinephrine, 5-HT, and Tyramine.
p.11
Clinical Applications of Antidepressants
What is the primary indication for Bupropion?
Major Depressive Disorder (MDD) including seasonal (winter) depression.
p.3
Clinical Applications of Antidepressants
What is the role of hormone replacement therapy in mood improvement?
Hormone replacement therapy can improve mood and depressive symptoms in both men and women.
p.9
Adverse Effects and Drug Interactions
What autonomic effects can occur with antidepressant agents?
Hypertension, tachycardia, and diaphoresis.
p.1
Major Depressive Disorder (MDD) Characteristics
What are some other characteristics of MDD?
Sleep disturbance, appetite disturbance, cognitive deficit, energy deficit, thoughts of guilt, worthlessness, and suicidal thoughts.
What is the effect of food on the absorption of Vilazodone?
Absorption increases with a fatty meal.
p.4
Clinical Applications of Antidepressants
What is a common use for Venlafaxine and Desvenlafaxine aside from depression?
Pain disorders (e.g., neuropathies, fibromyalgia).
p.8
Antidepressant Classes and Mechanisms
What is the primary use of Monoamine Oxidase Inhibitors (MAOIs)?
Depression unresponsive to other agents.
p.1
Pathophysiology of Depression
What is the effect of reserpine on monoamines?
Reserpine depletes monoamines and is associated with depression.
p.4
Adverse Effects and Drug Interactions
What are common noradrenergic effects of SNRIs?
Increased blood pressure and heart rate.
p.8
Adverse Effects and Drug Interactions
What is a common adverse effect of MAOIs?
Orthostatic hypotension and weight gain.
What is the mechanism of action of Mirtazapine?
Presynaptic α2 autoreceptor antagonist that enhances NE and 5-HT release.
p.2
Pathophysiology of Depression
What effect do Trp-free diets have on relapse in depression?
They decrease the likelihood of relapse.
p.11
Adverse Effects and Drug Interactions
What is a significant risk associated with TCAs and MAOIs?
Potentially lethal in overdose and serious drug interactions.
What is the dosing requirement for SSRIs and SNRIs?
Starting dose is the therapeutic dose; no titration required.
p.2
Neurotransmitter Involvement in Depression
What is the effect of the long allele of the serotonin transporter gene?
It provides resistance to stress and increases response to serotonergic antidepressants.
p.3
Clinical Applications of Antidepressants
What are some other uses of SSRIs besides depression?
SSRIs are used for Generalized Anxiety Disorder (GAD), PTSD, OCD, panic disorder, PMDD, and bulimia.
p.5
Major Depressive Disorder (MDD) Characteristics
What is the primary indication for 5-HT2 receptor modulators?
Major Depressive Disorder (MDD).
p.9
Clinical Applications of Antidepressants
How long should a therapy trial for antidepressants last?
8-12 weeks at therapeutic doses.
p.5
Neurotransmitter Involvement in Depression
What is the primary metabolite of Trazodone and its effect?
The primary metabolite is m-chlorphenylpiperazine (m-cpp), which is a potent 5-HT2 antagonist.
What are the pharmacodynamics of TCAs?
They inhibit 5-HT and NE reuptake, resembling SNRIs in function.
What are the primary pharmacodynamic actions of SNRIs?
They bind both SERT and NET.
p.4
Adverse Effects and Drug Interactions
What is a notable adverse effect of Venlafaxine in its immediate release form?
Dose-related increase in blood pressure.
p.2
Pathophysiology of Depression
What is the relationship between catecholamines and relapse in depression?
Decreased catecholamines increase the likelihood of relapse.
p.2
Neurotransmitter Involvement in Depression
How does the serotonin transporter gene affect vulnerability to MDD?
Homozygous (short) allele increases vulnerability to MDD and suicidality in response to stress.
p.3
Selective Serotonin Reuptake Inhibitors (SSRIs)
What is the prototype Selective Serotonin Reuptake Inhibitor (SSRI)?
Fluoxetine is the prototype SSRI.
How do secondary amine TCAs differ from tertiary amine TCAs?
Secondary amine TCAs, like Desipramine and Nortriptyline, lack active metabolites and have fairly linear kinetics.
p.9
Clinical Applications of Antidepressants
What is the goal of acute treatment for depression?
Remission of all symptoms.
p.1
Pathophysiology of Depression
What role does brain-derived neurotrophic factor (BDNF) play in depression?
BDNF is critical for neuronal survival, growth, and regulation of neural plasticity.
p.2
Adverse Effects and Drug Interactions
What are the limitations of using ketamine for long-term depression treatment?
Cognitive, dissociative, and psychomimetic properties.
p.2
Pathophysiology of Depression
How does clinical hypothyroidism relate to depressive symptoms?
It often presents with depressive symptoms that resolve with thyroid hormone supplementation.
What is a unique pharmacokinetic feature of Vortioxetine?
Extensively metabolized by CYP2D6 and other enzymes.
p.2
Antidepressant Classes and Mechanisms
What do all classes of antidepressants enhance?
Synaptic availability of serotonin (5-HT), norepinephrine (NE), or dopamine (DA).
What is the significance of norfluoxetine in relation to fluoxetine?
Norfluoxetine is the active metabolite of fluoxetine and has a longer half-life.
What is a significant drug interaction concern with TCAs?
Concurrent administration with CYP2D6 inhibitors can lead to increased TCA levels.
p.3
Adverse Effects and Drug Interactions
What is discontinuation syndrome in the context of SSRIs?
Discontinuation syndrome occurs with the sudden discontinuation of short half-life SSRIs, leading to withdrawal symptoms.
p.2
Antidepressant Classes and Mechanisms
What is the role of ketamine in depression treatment?
It is a potent NMDA receptor antagonist with rapid antidepressant effects.
p.8
Antidepressant Classes and Mechanisms
What are the two main classes of MAOIs?
Hydrazine derivatives and Non-Hydrazine derivatives.
What is the pharmacokinetic characteristic of Selegiline?
Available transdermal and sublingual to bypass gut and liver, reducing risk of food interactions.
