Antidepressants Flashcards
What do the symptoms of MDD reflect changes in?
Norepi
Serotonin (5HT)
Dopamine
Hospitalization of MDD patients is based on:
- Suicide risk
- Physical state of health
- Support system
- Presence of psychotic features
Treatment phases of MDD
- Acute: lasts 6-8 wks, goal is remission of symptoms
- Continuation: lasts 4-9 mos, eliminate residual symptoms and prevent relapse
- Maintenance: lasts 12-36 mos, goal is to prevent recurrence
Response to antidepressants
- 65-70% of pts improve
- Well documented placebo effect
- ADEs may occur immediately
- Resolution of symptoms may take 2-4 wks or longer
- Adherence is essential to success
Black box warning of antidepressants
ALL carry warning of increased suicidality risk in 18-24 yo during initial stages of treatment
How do TCAs work?
- Potentiate activity of NE and 5HT via reuptake blockade
- Block M1, a1, H1 receptors
What can TCAs be used to treat besides depression?
- Enuresis
- Migraines
- Nausea w/chemo
- Neuralgia
- Urticaria
- OCD
Which TCAs block 5HT reuptake more than NE reuptake?
Amitriptyline
Clomipramine
Which TCAs block NE reuptake more than 5HT reuptake?
Desipramine
Nortriptyline
TCA metabolism?
Hepatic - CYP1A2, 3A4, 2D6
TCA ADEs
- Tachy
- Orthostatic hypotension
- Cardiac rhythm changes
- Wt gain
- Sedation
- Lowers seizure threshold
- Sexual dysfunction
- Narrow therapeutic index
How do tertiary amine TCAs compare to secondary amine TCAs?
- More pronounced anticholinergic, antihistaminergic, hypotensive effects
- Avoid in elderly due to postural hypotension, risk of fall, and other CV effects
TCA contraindications
- BPH
- Closed angle glaucoma
- Cardiac disease
- Hepatic impairment
- Elderly
TCA drug interactions
- Avoid other CYP450 drugs
- May increase vasopressor response to direct acting sympathomimetics
- Additive adverse effects w/other agents w/serotonergic, anti-ACh, sedative or hypotensive properties
Examples of MAOIs
Phenelzine
Tranylcypromine
Selegiline transdermal patch
How do MAOIs work?
Block metabolism of NE, 5HT, DA via inhibition of MAO enzyme
Common ADEs of MAOIs
- Orthostatic hypotension
- Dizzy
- Mydriasis
- Edema
- Piloerection
- Tremor
- Wt gain
- Insomnia
Rare ADEs of MAOIs
Allergic reactions
Hepatic dysfunction
Blood dyscrasias
Describe hypertensive crisis caused by MAOIs
- Occurs after ingestion of tyramine containing foods/drugs
- Tyramine is metabolized in gut by MAO enzymes (causes release of NE from presynaptic sites)
- Medical emergency
- HTN, occipital HA, neck stiffness, diaphoresis
What MAOI does not require as much dietary restriction?
Selegiline transdermal patch at 6 mg/24 hrs
MAOI drug interactions
- Drugs that can precipitate HTN crisis (ephedrine, pseudoephedrine, phenylephrine)
- Serotonin syndrome w/other antidepressants, narcotics
When is a washout period of 14 days required?
Switching from one MAOI to another antidepressant
Switching from other antidepressant to an MAOI
When is a 5 wk washout period required?
Switching from fluoxetine to an MAOI
Switching from MAOI to another antidepressant requires a ___ washout period
14 days
Switching from fluoxetine to an MAOI requires a ____ washout period
5 week
SSRI agents:
- Fluoxetine
- Sertraline
- Paroxetine
- Citalopram
- Fluvoxamine
What is Fluvoxamine and what is it FDA approved for?
SSRI
FDA approved ONLY for OCD
Which SSRI is only approved for OCD use?
Fluvoxamine
What is 1st line pharm treatment of MDD?
SSRI
What can SSRIs be used for besides MDD?
- Anxiety disorders (OCD, PTSD, GAD, etc.)
- Bulemia
- Premenstrual Dysphoric Disorder
Common ADEs of SSRIs
- Nausea
- HA
- Sleep disturbances
- Agitation/anxiety
- Sexual dysfunction
- Tremor
Why are SSRIs more favorable than TCAs or MAOIs?
Less sedating and cause less weight gain
Overdose of SSRIs?
Not lethal
What is discontinuation syndrome of SSRIs?
- Potential for withdrawal w/abrupt d/c of short acting SSRIs
- Vivid dreams/nightmares, tremor, dizzy, crying spells, nausea, poor concentration
- Occurs as early as 1-4 days or up to 25 days after d/c
- Taper dose slowly over 7-10 days
How should SSRIs be d/c?
Taper dose slowly over 7-10 days to avoid discontinuation syndrome
How should most SSRIs be administered?
Recommended morning dosing d/t “energizing” effect
Which SSRI can be dosed in morning or evening?
Paroxetine (depending on pt response)
Fluoxetine drug interactions
- 5 wk washout before starting MAOI (2 wk for all other SSRIs)
- Potent inhibitor of CYP2D6
- Weak inhibitor of CYP3A4 and 2C9 (phenytoin, warfarin)
Sertraline drug interactions
Weak inhibitor of CYP2D6 at low doses (becomes more potent at higher doses, but still weaker than fluoxetine and paroxetine)
Paroxetine drug interactions
Potent inhibitor of CYP2D6
Citalopram and escitalopram drug interactions
Possible dose dependent inhibition of CYP2D6
Fluvoxamine drug interactions
- Potent inhibitor of CYP1A2
- Weak inhibitor of CYP2C9
What are mixed 5HT/NE reuptake inhibitors?
Venlafaxine
Duloxetine
Desvenlafaxine
How does Venlafaxine work?
- Potent 5HT/NE reuptake inhibitor
- At lower doses, much higher 5HT reuptake inhibition
- Weak DA reuptake inhibitor
Describe Venlafaxine
- Mixed 5HT/NE reuptake inhibitor for MDD
- XR formulation is considered 1st line agent for MDD
Metabolism of Venlafaxine
Substantial 1st pass via CYP2D6
ADEs of Venlafaxine
Similar SE profile to SSRIs
Venlafaxine drug interactions
- Weak inhibitor of CYP2D6
- Serotonin syndrome
How does Duloxetine work? What is it indicated for?
- Balanced reuptake inhibitor of 5HT and NE
- FDA approved for MDD, diabetic neuropathy, fibromyalgia
Which antidepressant is FDA approved for MDD, diabetic neuropathy and fibromyalgia?
Duloxetine
What is Bupropion (Wellbutrin)?
- Potent DA reuptake inhibition
- Very low reuptake inhibition of NE
Indications for Bupropion (Wellbutrin)?
Depression
Smoking cessation
Which antidepressant is indicated for smoking cessation?
Bupropion (Wellbutrin)
Bupropion drug interactions
- Use caution w/drugs known to lower seizure threshold
- Use w/MAOI is CONTRAINDICATED
- Very low inhibition of CYP2D6
What is Nefazodone?
- 5HT2 blocker AND reuptake inhibitor
- NOT a 1st line agent for depression
Nefazodone ADEs
- Black box warning: cases of life threatening hepatic failure
- Potent CYP3A4 inhibitor
Describe Trazodone
- 5HT2 blocker AND reuptake inhibitor
- Uncommonly used in depression (d/t ADEs)
- Commonly used as sedative
- Rare cases of priapism, QTc prolongation
What is Mirtazapine?
Selective, presynaptic a2 receptor antagonist (enhancement of NE transmission)
Mirtazapine ADEs
- Sedation
- Dry mouth
- Constipation
- Increased appetite, weight gain
Mirtazapine drug interactions
- Other sedating agents
- MAOIs
Rare ADE of Vilazodone
May cause new or worsening cataracts with long term use
Describe Levomilnacipran
- SNRI (higher selectivity for NE than 5HT)
- Primarily excreted by kidneys
- Role in treatment of depression is unknown (only studied vs. placebo)
Describe Vortioxetine
- 5HT reuptake inhibitor and agonist
- Role in depression treatment is unknown
- MC ADEs: NV, constipation
St. John’s wort in the treatment of depression?
- Found to be safe and effective for mild-mod depression
- NOT FDA regulated though
- Significant drug interactions (potent CYP3A4 inducer)
How does ECT work?
- Small current used to induce a seizure
- 30-60 secs in duration
- Pts are given sedative and paralytic
- 6 to 12 treatments (2-3 times per week)
Indications for ECT?
- High suicide risk
- Rapid physical decline
- Drug non-response or intolerability
- History of prior response to ECT
Contraindications to ECT?
NO absolute contraindications
Limitations/ADEs of ECT
- High relapse rate
- Impairments in memory and neurocognitive function
- Treatment-emergent mania
- HA, nausea, muscle aches
Describe depression in the elderly
- Often mistaken for another disorder (e.g. dementia)
- Depressed mood may be less prominent than other symptoms
- Increased suicide attempts
- Start LOW and go SLOW
Depression treatment in pregnant/lactating patients
- New evidence for potential resp distress and withdrawal syndrome in neonates whose mothers took SSRIs during pregnancy
- ECT can be used safely during pregnancy
- Sertraline and paroxetine appear in low concentrations in breast milk
How is response to antidepressants measured?
- Non-response: less than 25% decrease in baseline symptoms
- Partial: 26-49% decrease
- Partial remission: over 50% decrease
- Remission: return to baseline functioning
What is considered an adequate trial of antidepressants?
6-8 weeks at a maximum dosage
up to 12 wks in elderly
How to prevent relapse with antidepressant treatment?
Continue at full therapeutic dose for 4-9 months after symptom remission (aka continuation therapy)
When is lifelong maintenance therapy recommended in depression?
Patients with high risk of recurrence (2 or more previous episodes)
Define treatment resistant depression
Remission not achieved after 2 optimal antidepressant trials (6-8 wks)
Approaches to treatment resistant depression
- Switch to another SSRI or antidepressant w/different MOA
2. Augment w/another antidepressant, Li, T3, atypical antipsychotic, ECT, psychotherapy
