Depression Flashcards
Antidepressant Class BBW
Increased risk of suicidal thoughts and behaviors in young adults 18-24 years of age (and younger children or teens) especially at the early stage of treatment.
What to do?
• Counsel patients/families to monitor closely at beginning of treatment
• Possible ADRs could include agitation
• Deal with the subject of suicide directly
• Get help immediately
Which CYP enzymes are most involved in SSRI/SNRI metabolism? How about antipsychotics?
CYP2D6 - SSRI, SNRI
CYP1A2 - Antipsychotics
SSRIs (name the agents)
Citalopram (Celexa)
Escitalopram (Lexapro)
Fluoxetine (Prozac)
Fluvoxamine (Luvox)
Paroxetine (Paxil)
Sertraline (Zoloft)
SNRI (name the agents)
Desvenlafaxine
Duloxetine
Venlafaxine
Levominacipran
Serotonin Modulators (name the medications)
Gepirone
Nefazodone
Trazodone
Vilazodone
Vortioxetine
Tricyclic Antidepressants (TCAs) and other norepinephrine reuptake inhibitors
Amitriptyline, amoxapine, clomipramine, desipramine, doxepin, imipramine, maprotiline, nortriptyline, protriptyline, trimipramine
Monoamine Oxidase Inhibitors (MAO-I) (name the agents)
Selegiline
Rasagiline
Phenelzine
Tranylcypromine
Miscellaneous Antidepressant Agents (name the medications)
Brexanolone
Bupropion
Esketamine
Mirtazapine
Zuranolone
Second Generation Antipsychotics (SGA) Agents with MDD FDA Approval
All also have schizophrenia FDA approval! All but Rexulti also have Bipolar Disorder
Aripiprazole (Abilify)
Brexpiprazole (Rexulti)
Olanzapine (Zyprexa) - Only approved for MDD if used with Fluoxetine (Prozac)
Quetiapine (Seroquel)
None of these agents are to be used alone, they should be used with an antidepressant
Comparative Efficacy of Antidepressants. Which work best?
All antidepressants are considered equally efficacious for treatment of MDD; other factors should guide the selection of treatment options
Antidepressant Pharmacological Issue - Antidepressant Use in Bipolar Disorder
Unopposed use of AD in pt with underlying BPD (bipolar disorder) may precipitate a manic/mixed episode
Beware of a spontaneous recovery <2 weeks of starting the new agent as these agents take a while to work. May mean the pt has BPD or something else
General Approach to Treatment
• Psychotherapy considered for mild/moderate depression and psychoeducation a key component for all patients
• First line medication: SSRI, SNRI, bupropion, mirtazapine, vortioxetine
• If response to treatment (50% reduction of symptoms) has been reported after 4 weeks, AD should be continued at an optimal dose and reevaluated at 6, 8 and 12 weeks
• If symptoms persist after an adequate trial (4-8 weeks) at an adequate dose, guidelines suggest:
– Switching to alternate antidepressant (AD) OR AUGMENTING with an AD with an alternative MOA, a second generation antipsychotic (SGA) or psychotherapy
How to discontinue SSRIs
Taper if possible (except fluoxetine with long t1/2).
Discontinuation Syndrome can cause “electric shock sensations”
SSRI Class Effect - Rare, Serious ADEs (2 of many)
Hyponatremia and SIADH (rare but serious); monitor for increased lethargy mental status changes and serum sodium less than 135mEq/L
SSRI Patient Education / Therapy Adjustment Decisions
• Insomnia or sedation
– take in morning or switch to another with less insomnia
• Sexual dysfunction
– may need to switch to another agent such as bupropion
• Serotonin syndrome counsel on symptoms
– Mental status changes
– Autonomic instability
– Neuromuscular abnormality
– GI symptoms
Patient Education - How to Avoid Serotonin Syndrome
• Avoid concomitant use of serotonergic drugs
• Others:
– Triptan migraine agents
– Pain medications: fentanyl and tramadol
– Nausea products: zofran and reglan
– Buspirone
– Linezolid
– Ritonavir
• Drugs that impair the metabolism of serotonin
SSRIs other DDIs other than Serotonin Syndrome
– QTC prolongation with concomitant medications
– Increased risk of bleeding for patients on NSAIDS, anti-platelets and anticoagulants
SSRIs - Other Issues
– SSRI/SNRI hyponatremia (SIADH)
– Sexual side effects
– Withdrawal syndrome
– Generally require caution/dose modifications with hepatic impairment (renal is less common, but confirm status)
Universal SSRI precautions
Discontinuation syndrome (except fluoxetine b/c longer half life), abnormal bleeding due to 5-HT reuptake on platelets, hyponatremia, serotonin syndrome, potential cognitive and motor impairment.
Most have some degree of QTc prolongation effects.
More likely energy boosting than sedating
Citalopram
SSRI
Doses >40mg not recommended (older adults 20mg)
FDA released QTc warning in 2023
Available as ODT
Maximum Daily Dose 20mg for:
- Those 60 years or older
- CYP 2C9 PM
- Hepatic Impairment
Escitalopram
SSRI
Benefit of 20 mg over 10 mg not established
Isomer of citalopram
Currently not labeled with same FDA QTc warning and dose requirements as citalopram - still not safest agent for patients with this risk
Maximum Daily Dose: 10mg for hepatic impairment
Pediatric Approved Dosing: 12-17 years old
Maximum Daily Dose of 10mg for Hepatic Impairment
Fluvoxamine
SSRI
Caution in Elderly - one of the most sedating, also can be anticholinergic (less tolerable than many other agents)
Many drug interactions (CYP 1A2) - recall CI with Ramelteon from sleep lectures
Fluoxetine
SSRI
• Majority of patients will not require >20 mg/d
• 40 mg/day or more should be divided in 2 or more doses
• Only SSRI approved for once weekly administration
• Available as liquid
• Inhibits CYP 2D6 (TCAs), CYP 3A4 (carbamazepine)
• Anorexia
• Anxiety and Insomnia
Paroxetine
SSRI - Paxel
• Short half-life but CR available
• sedating & anticholinergic careful in the elderly
• Avoid in pregnancy
• Akathisia
• Reports of bone fracture
Sertraline
SSRI - Zoloft
Concentrate can be mixed with ONLY water, ginger ale, lemon/lime soda, lemonade or orange juice
SNRI Class Adverse Effects
Abnormal bleeding due to 5-HT reuptake on platelets, potential for increased risk of activation of mania, elevated blood pressure, hyponatremia and serotonin syndrome and discontinuation syndrome. Tend to be more energy boosting than other AD
Also share with SSRI: serotonin syndrome, variable seizure and QTc risks bleeding risk, hyponatremia, anticholinergic effects (glaucoma, urinary retention, etc)
MAOi Class Adverse Effects
Must wait 4 to 5 half-lives of drug or active metabolite after D/C interacting drug: for example:
• Fluoxetine and Vortioxetine have the longest T1/2 of the SSRIs so need to wait longer than 2 weeks before start of an MAOI
– Fluoxetine: 5 weeks
– Vortioxetine: 3 weeks
• Dietary restrictions of Tyramine Containing foods
– Aged products, smoked and pickled products, yeast extracts
– Risk life threatening hypertensive crisis
• Other side effects: postural hypotension, diarrhea, anticholinergic drying effects, sexual dysfunction
• Monitor for potential DDI-primarily related to hypertensive crisis risk:
– Amphetamines, decongestants, methylphenidate…
• Serotonin syndrome
– dextromethorphan, etc
Irreversible nature of the medication
• Clinician should wait 2 weeks before switch to new drug
• Typically reserved for ‘last resort’
Nefazodone
Serotonin Modulator
Hepatic BBW
Risk of priapism
Trazodone
Serotonin Modulator
Sedating
Risk of priapism
More anticholinergic and bleeding risk compared to nefazodone
Vortioxetine (Trintellix)
Serotonin Modulator
Reduce dose by 50% for CYP2D6 poor metabolizers
Long half life (recall: 3 weeks off this agent before starting MAOi)
Gepirone
Serotonin Modulator approved for MDD
High Fat meals increase absorption - counsel to keep meals consistent
Extensively metabolized by CYP3A4
• Dosing alerts for:
– Older adults
– Hepatic impairment (but severe=CI)
– Renal impairment
Shares universal precautions: FDA boxed warnings for suicide, QTc prolongation, serotonin syndrome, MAO washout
(New agent) May offer improvement: reduced sexual side effects, less weight gain
Bupropion
Miscellaneous Antidepressant
Many brand names with different uses
Wellbutrin CONTRAINDICATED in patients with risk of SEIZURE or seizure disorder
Caution in patients with eating disorders or alcohol use disorders (because electrolyte abnormalities)
Hypertension, insomnia, activation and anxiety, neuropsychiatric events with smoking cessation (warnings downgraded)
Mirtazapine (Remeron)
Miscellaneous Antidepressant
Sedating
Cholesterol elevation
Significant weight gain (>7%) common - stimulates appetite
ODT option
Transaminase increases possible - monitor LFTs
Agranulocytosis has been reported
Sometimes better for older adults because of these adverse effects
Esketamine (Spravato)
Miscellaneous Antidepressant - Nasal Spray
C3 Scheduled Controlled Substance
Indicated for Treatment Resistant Depression in adults in combination with an antidepressant
– Failure of at least two other drugs required
• Non-competitive N-methyl D-aspartate (NMDA) receptor antagonist
• CI: history of aneurysmal vascular disease, and intracerebral hemorrhage
• Can lead to increased blood pressure, cognitive impairment, impaired ability to drive or operate machinery, embryo-fetal toxicity
• Boxed warning: Sedation, dissociation; abuse and misuse; suicidal thoughts and behaviors
• Adverse reactions: dissociation, dizziness, N/V, sedation, vertigo, hypoesthesia, anxiety, lethargy, increased blood pressure, and feeling drunk
• Only available through the SPRAVATOR REMS program
– Dispensed in a REMS certified healthcare setting to patients enrolled in the program
– Administered in the direct observation of a healthcare provider
– Monitored for two hours after administration
– Pharmacies must be certified by REMS and only dispense to REMS certified healthcare facilities
Zuranolone
Zurzuvae
Used to treat postpartum depression
• Can be used alone or as an adjunct to oral antidepressant therapy
• 50 mg taken orally once daily in the evening for 14 days
• Administer with fat-containing food (e.g., 400 to 1,000 calories, 25% to 50% fat)
Boxed warning: Advise patients not to drive or engage in other potentially hazardous activity until at least 12 hours after administration
Brexanolone
Zulresso
Used to treat postpartum depression
IV continuous infusion given over 60 hours (2.5 days)
Hypoxia - monitor via continuous pulse oximetry, D/C if profound hypoxia occurs
Excessive Sedation - monitor q2h during wake hours. D/C infusion until symptoms resolve then resume at same or decreased dose PRN
Which Medication Class to avoid in:
Seizure Disorders?
Substance Abuse?
Cardiac Complications?
GI Bleeding and Anticoagulation?
Bupropion
Benzodiazepines
TCAs
SSRIs
Elderly Population Treatment of Depression
• SSRI usually best choice as initial treatment
• Second choices often bupropion and venlafaxine
• Evidence of mirtazapine benefits on anxiety, sleep, and appetite
stimulation (watch cholesterol)
• Avoid TCA
Elderly BEERS List
Chronic Seizures or Epilepsy - Bupropion
Delirium - All TCAs
History of Fractures/Falls - TCAs and SSRIs
Children Depression Treatment Options
Fluoxetine is the only medication approved for tx of children 8 years and older as well as for adolescent depression
Escitalopram is FDA approved for children over 12 years old
Pregnancy Treatment of Depression
Pregnancy does not protect against depression and untreated, can result in relapses
SSRIs are the most commonly used and best tolerated medication during pregnancy, but these too carry a small but significant risk (AVOID PAROXETINE)
Augmentation Agents
Lithium - first line augmenting agent (best studied by augmenting TCAs)
Triiodothyronine - used regardless of thyroid status, but may cause hyperthyroidism
SGAs
Buspirone, stimulants (mixed results with these)
Neuroleptic Malignant Syndrome (NMS) vs. Serotonin Syndrome (SS)
NMS:
• Dopamine antagonists
• Onset variable ~1-3 days
• Lead pipe rigidity in all muscle groups
• Hyporeflexia
• Normal pupils
• Normal or decreased bowel sounds
• Increased CPK values
SS:
• Serotonin agents
• Onset variable < 12 hours
• Hyperreflexia, clonus
• Dilated pupils
• Hyperactive bowel sounds
