Antidepressants, Mood Stabilizers, and Medications to Treat Anxiety Flashcards
What features of depression might make you want to learn more towards psychotherapy than pharmacotherapy?
- Presence of personality disorders
2. Psychosocial stressors -> medication cannot fix this
What features of depression might make you want to learn more towards pharmacotherapy than psychotherapy?
- History of response to medications in the past
- Family history of major depressive disorder
- Moderate to severe depression -> medications will always be needed
What is the mechanism by which antidepressants take 4-8 weeks to fully work?
Inhibitory 5-HT1A receptors are over-expressed on dendrites of serotonergic neurons in depression. Thus, they do not adequately release serotonin.
Over time of SSRI treatment, the 5-HT1A receptors become downregulated due to large amounts of serotonin in the area. This downregulation allows the increased release of 5-HT to the synapse.
This is called neuronal disinhibition
Other than for elderly patients, when should you start out with a low dose of antidepressant?
Patients with anxiety -> initial few doses can cause anxiety
What condition, if left untreated, can decrease the effectiveness of an antidepressant and must be addressed?
Insomnia
What are some of the withdrawal symptoms of SSRIs?
Dizziness, nausea, paresthesias, anxiety, insomnia
-> must be tapered over 2-4 weeks
What is the black box warning on antidepressants?
They increased suicidal thoughts and behavior (suicidality) in all people under age 24 in short term MDD / other psych disorder.
What is the only SSRI which has a recommendation of not being safe in pregnancy? What can it cause?
Paroxetine - can cause cardiac malformations in 1st trimester
List the four major SNRIs - only one of these you are unlikely to know?
Venlafaxine
Desvenlafaxine
Duloxetine
Levomilnacipran - Fetzima
List the atypical antidepressants. There is one which you are new to.
Bupropion Mirtazapine Trazodone Vilazadone **Vortioxetine**
What medication class are doxepin and amoxapine in? What do other ones in this class end in?
Tricyclic antidepressants
-Others end in -amine, tyline, or tiline
What class is isocarboxazid in and what are some others in this class?
MAOIs
Phenelzine
Tranylcypromine
Selegiline
In regards to dosing, why are SSRIs preferred to other classes of antidepressants?
- They have a wide therapeutic window -> no need to closely titrate.
- They can be started at therapeutic dose (vs TCAs / MAOIs which need titration)
- They are safe in overdose
Which is the top SSRI known to be activating or sedating and what should be done to minimize this side effect? What drug is associated with the most weight gain?
Activating - Fluoxetine (one with longest halflife) -> dose in morning when you need the energy
Sedating - Paroxetine - give at bedtime
Weight gain - Paroxetine
What should be done to curb sexual side effects of SSRIs?
Lower the dose or add medication (bupropion, except in anxiety)
Which SSRI has the most CYP interactions, and which SSRIs are known to interfere with opiates?
Fluvoxamine - most interactions
Fluoxetine and paroxetine - interferes with effectiveness of opiates like codeine via CYP2D6 interference blocking conversion to active form
What additional functionality do SNRIs have and what side effect does this add?
NE reuptake blockade which is good for management of chronic pain syndromes
Added side effect - hypertension
Why does bupropion not have any sexual side effects? Is it useful in anxiety or any other conditions?
It is an NDRI, with no serotonergic effects which cause sexual dysfunction
Bad in anxiety -> can exacerbate
Useful in smoking cessation
What is the side effect of concern for bupropion / contraindication?
Seizures at higher doses
-> contraindicated in bulimics and anorexics likely to have underlying electrolyte imbalances
What is the mechanism of action of mirtazapine? Include all relevant receptors and their effects
Noradrenergic and specific serotonergic antagonist (NaSSA)
- blocks 5-HT2 and 5-HT3 receptors (increases 5-HT1 agonism overall), with fewer sexual / GI side effects
- blocks alpha2 receptors - increases NE in the synapse
- histamine antagonism - increases weight gain and sedation
What is the mechanism of action of Vilazodone? What is its increased side effect?
SPARI - Serotonin partial agonist / reuptake inhibitor
SSRI + 5HT1A agonist -> possible increased efficacy for anxiety / depression
May make GI side effects worse
What is the mechanism of action of trazodone?
SARI - Serotonin antagonist / reuptake inhibitor
- SSRI plus antagonizes 52 - 5HT-2 receptors
- also has anti alpha-1 (lighter) and anti-histamine (beeswatting on the bench) effects
What is the usefulness of trazodone and its side effect profile?
Useful for insomnia due to anti-histamine effects
Alpha-1 blockade - can cause orthostatic hypotension (coach fainting)
Also causes priapism (erect trombone)
What is the mechanism of action of Vortioxetine and why is it potentially better than other antidepressants?
SSRI + a number of agonist / antagonist effects
- 5HT7 blockade my confer some advantage to patients with cognitive complains over other SSRIs
What is the overall mechanism of tricyclic antidepressants?
Inhibition of NE reuptake, with varying degrees of SRI activity
ALL antagonize alpha1, histamine, and muscarinic ACh receptors
What syndromes might TCAs be particularly useful for?
Pain syndromes: migraines / neuropathy, due to NRI effects
Enuresis: Due to anticholinergic effects
Which TCAs are thought of as primarily NRIs? Primarily SRIs?
Nortriptyline (tripping child) and desipramine (imprint) - primarily NRIs
Clomipramine - primarily SRI -> has a specific usefulness
What cardiac side effects does a patient need to look out for when starting a TCA? What should be done when starting a patient?
Look out for chest pain / shortness of breath
Need baseline EKG if older than 40 or history of CVD
-> can cause tachycardia / prolonged QT / ST depression even at therapeutic doses
What are the drug interactions of concerns with TCAs?
They do not interact with CYP system, but should be not combined with other things potentiating their offtarget effects (anticholinergics, antihypertensives, CNS depressants)
What are the 3 C’s of TCA overdose?
Coma
Convulsions (seizures)
Cardiotoxicity (QT prolongation, arrhythmias)
What is the specific mechanism of action of all MAOI antidepressants in the US?
All MAOIs are irreversible and nonselective (block both A and B, take 2 weeks to reproduce the enzyme)
What type of depression are MAOI’s useful for?
Atypical depression, characterized by sleeping too much, eating too much, leaden paralysis, mood reactivity, and rejection sensitivity
What are the possible overdose side effects of MAOIs which limit their use?
Hypertensive crisis (tyramines broken down by MAO-A primarily in gut, + NE breakdown blockade) Serotonin syndrome
What are the common side effects of MAOIs?
Edema
Insomnia
Sexual dysfunction and orthostatic hypotension (alpha1 blockade)
Weight gain (think of eating too much cheese)
What is the definition of a hypertensive crisis and what is the treatment? What are a few symptoms?
Diastolic blood pressure is greater than 120 mmHG
Alpha-antagonist phentolamine is treatment
Symptoms: Occipital headache, neck stiffness, dilated pupils, and abnormal heart rate
What drugs should be avoided with MAOIs and what can they cause?
Any drugs with sympathomimetic activity, including decongestants, stimulates, and antidepressants with NRI activity
Can cause hypertensive crisis
How long do you have to wait after stopping a MAOI to start another 5HT agent? How longer after stopping fluoxetine to start a MAOI?
2 weeks after MAOI - enzyme turnover time
5 weeks after fluoxetine - has a long halflife
What are the features of serotonin syndrome?
Hyperthermia, hypertension (think of overheating boss with smoke coming from his ears), autonomic instability, hypertonicity and myoclonus (think of boss taping his food excessively)
What are the tricyclic compounds, opioids, and migraine medications which can precipitate serotonin syndrome when taken with MAOIs?
Tricyclic compounds
- > cyclobenzaprine
- > carbamazepine
Migraines
-> triptans (5HT1b/d)
Opioids (4 M’s + 1 other)
- > tramodol
- > methadone
- > dextromethorphan (oh god memo)
- > mepiridine
- > Propoxyphene
Why should MAOIs be given cautiously with anesthesia?
General and local anesthetics often contain epinephrine
Are dietary restrictions needed with selegiline? By what route will you not need it?
Yes, but not needed if given as EMSAM (transdermal patch)
-> only inhibits MAO-B at these doses, so an ineffective antidepressant
What nonpharmacologic therapy can be used alone or in combination with drugs for seasonal / nonseasonal depression?
Light therapy
What is ketamine good for and its main side effect of risk?
Good for 72-hour antidepressant action (Aside from its general anesthetic properties)
- > may cause hypertensive crisis
- > does not lead to lasting maintenance of antidepressant effects without further injections
When is ECT considered and how is it done?
With 2+ medication failures (generally more)
Patients who are acutely suicidal
Works via inducing seizures, works in 70% of treatment-resistant
What are the contraindications of ECT and side effects of concern?
Contraindications:
Recent MI (causes SANS / PANS discharge)
Space occupying / hemorrhagic cranial lesion (increases ICP)
Side effect:
Memory problems
What confers the greatest mortality risk in ECT?
Use of general anesthesia
What is used as an alternative to ECT in treatment-resistant patients which has less efficacy? Side effect?
Transcranial magnetic stimulation (TMS)
-> Electrical current depolarizes neurons over dorsolateral prefrontal cortex
-> can cause headache
What drugs / combinations are used to treat acute bipolar depression?
Atypical antipsychotic alone
Atypical antipsychotic / antidepressant (olanzapine / fluoxetine)
Lamotrigine
Lithium
What drugs are used to treat acute bipolar mania?
Atypical / typical antipsychotics
Carbamazepine / Valproic Acid
Lithium
What drugs are used for maintenance treatment of bipolar?
Atypical antipsychotics
Carbamazepine / Valproic Acid
Lamotrigine
Lithium
Can you summarize the therapeutic uses of lithium, anticonvulsants, atypical / typical antipsychotics for BPAD?
Lithium: Good for all three
Anticonvulsants (carbamazepine / valproic acid) -> sedating, good for mania and maintenance
Atypical antipsychotics - good for all three, often as adjuunct
Typical antipsychotics - only used in acute bipolar mania
What medication is known to decrease suicidality in bipolar patients, and what is its mechanism of action?
Lithium
Depletion of PIP to stop second messaging systems via G-protein
What is the therapeutic concentrations of lithium and when should this concentration be measured?
0.6 - 1.2 mEq/L
Should be measured 12 hours after last dose, every 6 months after maintenance has begun
How long does it take for lithium effects to be seen and what should be done in the meantime?
10-14 days, use antipsychotics or benzodiazepines to control agitation / insomnia
What levels of lithium are considered deadly and when should hemodialysis begin?
> 2.5 mEq/L
>2.0 = acute renal failure, need to begin hemodialysis. Seizures can occur far before this point
What drugs increase lithium levels? Where is it cleared?
NCAT - think MCAT but NCAT N - NSAIDs C - Calcium channel blockers A - ACE inhibitors T - Thiazide diuretics
N/A - reduce GFR via reduced blood flow or volume
T - reduce sodium levels, thus increasing reabsorption of lithium in PCT
It is 95% kidney-cleared, 80% is reabsorbed so 20% of lithium clearance approximates GFR
What drugs / conditions decrease lithium levels?
Theophylline / caffeine (increase GFR)
High sodium (larger Vd, less reabsorption of lithium)
Pregnancy (large Vd)
List the minor CNS, cardiovascular, dermatological, endocrine / metabolic, fetal, GI, hematologic, and renal side effects of lithium?
CNS - hand tremor / cognitive blunting Cardiovascular - Edema Dermatologic - alopecia, acne, psoriasis Endocrine / metabolic - weight gain Fetal - Ebstein's anomaly Hematologic - Benign leukocytosis Renal - Polyuria, polydipsia, nephrogenic diabetes insipidus
What are the more medically serious side effects of lithium?
Hypothyroidism is common
Irreversible kidney disease
ECG changes - SA node blockade and sick sinus syndrome
What is the mechanism of action of valproic acid and what is it used for in BPAD?
Increases GABA levels in the brain, along with Na+ channel inactivation, used for acute mania and maintenance treatment
What is the most likely drug-drug interaction of valproic acid, and should plasma concentration be monitored?
Most likely to interact with highly protein-bound meds like warfarin, digitalis, and other anticonvulsants
Should be monitored and held to 50-100 mg/mL
What blood-related and toxicity-related side effects differentiate valproic acid from lithium toxicity?
Valproate - will cause leukopenia / thrombocytopenia (vs lithium increases leukocytes), possible agranulocytosis
Valproate can also cause hemorrhagic pancreatitis (hemorrhagic sponge) and hepatotoxicity
What tests should be ordered for valproate which are not ordered for lithium?
Liver function tests (metabolized by liver, can cause hepatotoxicity)
Platelets (agranulocytosis is a concern)
Lithium is more thyroid / kidney oriented since it is metabolized by kidney
What is the mechanism of action of carbamazepine and its therapeutic window which requires monitoring?
Inhibition of voltage-gated Na+ channels
Therapeutic level is 8-12 mg/mL (Valproate was 50-100)
What are some of the more common and rarer side effects of carbamazepine?
Common:
Diplopia, ataxia, nausea
Less common but serious: Stevens-Johnson syndrome (along with lamotrigine), pancytopenia, hepatic / pancreatic failure (like valproate)
What is the teratogenicity of lithium, carbamazepine, valproate, and lamotrigine?
Lithium: Epstein’s anomaly (malformation of tricuspid valve)
Carbamazepine: NTDs
Valproate: NTDs
Lamotrigine: None
What symptoms are very worrying of SJS and what should be done if this occurs?
Rash which is associated with sore throat and fever or diffuse facial / mucosal involvement
-> go to the ER
What phases of bipolar disorder is lamotrigine indicated for? Its mechanism of action?
Inhibition of Na+ channels / glutamate channels
Approved for maintenance of BPAD, and sometimes treatment of bipolar DEPRESSION
What interactions and side effects does lamotrigine have?
Carbamazepine -> decreases lamotrigine levels by inducing CYP
Valproate -> increases lamotrigine levels by blocking CYP
What are the common and severe side effects of lamotrigine? who is most susceptible?
Common - Headache, nausea, dry mouth, ataxia, diplopia
Severe: SJS (toxic epidermal necrolysis) -> beningn rash is common early, but can be serious, titrate slowly especially if with valproic acid.
Kids more susceptible to SJS
Why is antidepressant use risky and BPAD, and what should be used to prevent these sequellae?
Can lead to manic episode (Reversal)
Use lamotrigine for depresison, or olanzapine / fluoxetine
What is the treatment for OCD?
HIGH dose SSRI or clomipramine (mostly SRI tricyclic) -> need that serotonin
What are the benzos with the most rapid onset and shortest half lives?
Rapid onset - Diazepam
Shortest halflife - Alprazolam
What are the side effects of benzos, especially as they relate to the elderly?
Cognitive problems / falls in elderly
Decreased respiration in prexisting pulmonary dysfunction
Anterograde amnesia
What benzos are the safest to use with the elderly and why?
Lorazepam, Oxazepam
-> glucuronidation is only required (phase 2 metabolism does not slow with age)
-> others require oxidation (phase 1) which does slow with age
What is the teratogenicity of benzos?
Has been associated with cleft palate in first trimester
What is the largest drug interaction of benzos?
Benzos and opiates -> combined respiratory depression, sleepiness, coma, and death
What beta-blocker is used in anxiety, what for, and how does it work?
Propanolol - for social anxiety disorder / social phobia, right before meeting that situation
Works by reducing peripheral manifestations of anxiety (tachycardia, tremor, sweating) to prevent conscious thought of it
What is one medication which is only approved for GAD? How does it work?
Buspirone - 5HT-1a agonist
What are the side effects of buspirone? Do you tolerize?
Mostly GI upset, drowsiness / dizziness
SEROTONIN SYNDROME IS POSSIBLE
-> cannot tolerize like benzos, but takes much longer to work (4-6 weeks)
