Pharmacology Quiz - Depression Treatment PDF

**First-line treatment for depression- SSRIs**  2. **SSRIs-individual characteristics noted for each**  **3. SSRIs-onset, side effects**  Onset: do not fully "bloom" until 4 to 8 weeks after being started.  GI symptoms: Nausea, vomiting, diarrhea  Changes in appetite: Weight loss/ gain  Sleep...

**First-line treatment for depression- SSRIs**  2. **SSRIs-individual characteristics noted for each**  **3. SSRIs-onset, side effects**  Onset: do not fully "bloom" until 4 to 8 weeks after being started.  GI symptoms: Nausea, vomiting, diarrhea  Changes in appetite: Weight loss/ gain  Sleep disturbances: Drowsiness with Fluvoxamine  Anxiety & Tremors (activation)  Sexual dysfunction: Loss of libido, delayed ejaculation  Discontinuation syndrome  **4. Examples of each class of antidepressant, major side effects and monitoring for each**  **MAOI: **  Phenelzine/Nardil, Tanylcypromine/Parnate, Isocarboxazid/Marplan, Selegiline. Risk of serotonin syndrome if treatment is overlapped. Avoid tyramine. Risk of hypertensive crisis. Avoid drugs that raise blood pressure. Wait 2-3 weeks after discontinuing MAOI before starting a serotonergic medication. If switching from SSRI to MAOI, wait 1 week for most (5 weeks for fluoxetine). Used mainly when other antidepressants have failed.   **TCA:** **-triptyline, -ipramine.** Sinequan (doxepin), Tofranil (imipramine), Anafranil (clomipramine), Elavil (amitriptyline), Pamelor (nortriptyline), Asendin (amoxapine). Overdose may be lethal\*; do not give to suicidal patient. ***widened QRS complex on EKG. Don't give to patient with heart problems. Sedation and weight gain due to blockade of H1. *** Blockade of α-1 adrenergic receptors-  Dizziness, Orthostatic hypotension, Drowsiness. Blockade of M1 muscarinic receptors (dry mouth, blurred vision, urinary retention). Good for sleep, migraine, neurogenic pain, chronic pain. Wouldn't give to someone old, unsteady, urinary retention. Educate about the side effects. TCAs antagonize **acetylcholine and histamine** which accounts for much of their side effect profile.  **SSRI**: [fluoxetine] (longest half life, can be activating, prevention of discontinuation syndrome, wait 5 weeks before starting another antidepressant, combine with olanzapine for bipolar depression); [sertraline] (good for PTSD);   [citalopram] (increased QTc prolongation);   [escitalopram] (cleanest SSRI in terms of drug interactions);   [paroxetine] (high side effect profile- weight gain, sexual SE, sedation, constipation, discontinuation effects, short half life. Avoid if patient is overweight/doesn't want to gain weight, concerned about sexual side effects);   [fluvoxamine] (OCD), strong CYP1A2 inhibitor;   [vilazodone] (SSRI + 5HT1A partial agonist, partial agonist at serotonin 1A autoreceptor; take with food!);   [vortioxetine/Trintellix] (5HT1A agonist-autoreceptor, good for anxiety, pro-cognitive effects, less sexual side effects  **SNRI:** increased risk of discontinuation syndrome. May use if no response to SSRI. Venlaflaxine (no significant action at NE sites at doses lower than 150mg);   Desvenlafaxine (Pristiq)- related to venlafaxine but acts on NE at all doses so can use lower dose (50mg) than venlafaxine; has not shown to be more effective at higher doses;   duloxetine (Cymbalta)- use for chronic pain, fibromyalgia, neuropathy  **Mirtazepine:** sedation, weight gain, increased appetite. Cancer, frail, elderly. Use in elderly patient who needs to gain weight. Can be combined with SNRI.   **Trazodone:** sedation (used as sleeping aid/hypnotic), risk of priapism! Trazabone  **NDRI:** bupropion- does not inhibit reuptake of serotonin. Fewer sexual side effects. Side effects: insomnia, tachycardia, and lowers seizure threshold (contraindicated in bulimia). Do not give to patients with seizures, alcohol abuse, bulimia. Can use in major depression and bipolar depression since it doesn't inhibit serotonin. Stimulating so don't take at night.     **5. Discontinuation syndrome and treatment**  When a serotonergic medication is stopped abruptly, this can lead to discontinuation syndrome (flu-like symptoms and general malaise, insomnia, nausea and GI upset, imbalance including vertigo and light-headedness, sensory disturbances such as tingling in the head ("brain zaps"), and hyperarousal (increased energy and anxiety. Educate patients on importance of not stopping medication abruptly. Discuss with provider and aim for slow taper and over several weeks or months.   Also may add fluoxetine to self taper.  Effexor, Cymbalta, SNRIs are bad for discontinuation syndrome    **6. Serotonin syndrome**  - **Signs/symptoms** Serotonin syndrome is a medical emergency and may cause:  - Diarrhea, shivering, muscle rigidity, hyperreflexia, fever, hyperthermia, vital sign instability (irregular or rapid heartbeat, hypertension, respiratory distress), encephalopathy, confusion, changes in mental status, pupil dilation, depressive disorder.   - **What causes it? What meds?** SSRIs, MAOI, TCAs, zofran. To tell difference in serotonin syndrome and NMS- find out what patient is taking.   If taking drugs that increase serotonin, concern for SS; Treat Serotonin syndrome with Cyproheptadine.  If taking antipsychotics, concern for NMS  **7. Vilazodone mechanism of action** Partial agonist at the 5-HT1A receptors. Absorption and bioavailability are reduced by half when taken on an empty stomach TAKE WITH FOOD \*\*\* Partial agonist actions at presynaptic somatodendritic serotonin 1A autoreceptors may theoretically enhance serotonergic activity and contribute to antidepressant actions, desensitize serotonin 1A autoreceptors \   **9. Targeting symptoms of depression with different agents**  SSRI's, SRNI's, or atypical antidepressants are reasonable 1st line treatments. In general, MAOIs and TCAs used after other options have been exhausted (d/t higher side effect burden and higher lethality in overdose).    If worried about weight, do not use mirtazapine.  If worried about sexual side effects, avoid SSRI's.   If often forget to take medications, consider fluoxetine.  If pregnancy, use sertraline.    **10. BDNF relationship with depression and SSRIs**  Decreased levels of BDNF are associated with increased depressive symptoms. SSRIs increase BDNF levels.  **11. Adverse effects**  - Acute dystonia- EPS. Sustained muscle contraction, laryngospasm, oculogyric crisis. May be mistaken for agitation or unusual stereotypic movements associated with schizophrenia. Caused by blockade of D2 in nigrostriatal pathway  - Akathisia- EPS. Restlessness (may be subjective), unable to sit still (rocking, pacing, constant motion of unilateral limb). May be mistaken for anxiety. Due to blockade of D2 in nigrostriatal pathway.   - Parkinsonism- EPS. tremors, rigidity, mask-like expression, shuffling gait. May be confused as affective blunting or emotional flattening. Due to short-term blockade of D2 in nigrostriatal pathway causing increased acetylcholine. Treat with benztropine, diphenhydramine, amantadine.  - Tardive dyskinesia- EPS. Involuntary abnormal muscle movement of facial, oral, trunk, extremities. Caused by chronic blockade of D2 in nigrostriatal pathway. All FGA can cause TD. Treat with VMAT2 inhibitor.  - Note: all EPS are in the nigrostriatal pathway due to D2 blockade  - Agranulocytosis- low neutrophils. Increased risk with clozapine. Serial ANC weekly for 6 months then biweekly. Discontinue med and give filgastram (colony stimulating factors)   - Hyperprolactinemia- increased prolactin due to blockade of D2 in tuberoinfundibular pathway. Increased risk with risperidone. Obtain prolactin level at baseline and at 3 months. Reduce dose, add aripiprazole   - Orthostatic hypotension- increased risk with Iloperidone. Due to blockade of alpha 1 adrenergic receptors.    **12. Antidepressants**  **13. Common medication side effects: contraindications, medication metabolism, monitoring, neurotransmission, common receptor binding mechanism of action, drug interactions **  **14. Multi-symptom treatment options using SSRIs, SNRIs, TCAs**  Mirtazepine + SNRI= increased efficacy for depression  Fluoxetine + olanzepine = bipolar depression  Lexapro + buspar = similar effects as vilazodone due to 5HT1A partial agonism  Vortioxetine + bupropion = decrease dose of vortioxetine (trintellix) by ½ because bupropion (wellbutrin) will increase serum levels of vortioxetine     **15. SSRIs and sexual side effects**  Citalopram, vortioxetine has less sexual side effects than other SSRIs  paroxetine = higher sexual side effects    **16. Switching to and from MAOI-time frame**  More danger of serotonin syndrome if initiated too fast because the monoamines are wiped out and your body takes about 2 weeks to rebuild the MAO transmitters so wait 2 weeks before initiating a SSRI  Have to also wash out SSRI before starting MAOI but not as long as washing out a MAOI.   If you went from MAOI first then to SSRI, wait two weeks so enzyme can regenerate  If SSRI to MAOI, wait for SSRI to get out of system: 1 week or 5 weeks                              **17. AIMS questions **  - **What is it used for - Assessing for tardive dyskinesia** AIMS is used to quantify severity of TD and should be considered as a regular and routine part of clinical management.  - **Which items are scored **    Score the highest amplitude or frequency in a movement on the 0-4 scale, not the average; \ - Score Activated Movements the same way; do not lower those numbers as was proposed at one time;  Items scoring 2 or greater in two or more areas suggest probable Tardive Dyskinesia (TD).  Scoring 3 or greater in one area suggests Tardive Dyskinesia (TD).    A POSITIVE AIMS EXAMINATION IS A SCORE OF 2 IN TWO OR MORE MOVEMENTS or a SCORE OF 3 OR 4 IN A SINGLE MOVEMENT              **18. Dopamine pathways**  **Excess/deficient, resulting effect**                                   1. nigrostriatal- involved with movement. Too little dopamine in this pathway leads to EPS (acute blockade) and TD (chronic blockade). Substantia nigra      2. mesolimbic- involved with emotion (limbic), positive symptoms (hallucinations, delusions) of psychosis from too much dopamine. D2 blockers work in this pathway to decrease dopamine levels and reduce positive symptoms     3. mesocortical- negative symptoms (emotional blunting, cognitive problems) due to too little dopamine     4. tuberoinfundibular- hyperprolactinemia. Too little dopamine increases prolactin (gynecomastia, galactorrhea, menstrual irregularities).              **20. Neuroleptic malignant syndrome **  - **Signs/symptoms**  - **Treatment**  Symptoms start days to weeks after starting medications (typically antipsychotics, as a reminder: 1st generation chlorpromazine, fluphenazine, Haloperidol, Perphenazine, Pimozide. 2nd generation: aripiprazole, brexpiprazole, risperidone, paliperidone, ziprasidone, olanzapine, quetiapine, iloperidone, asenapine, lurasidone, cariprazine, lumateperone    **F: fever**  **E: encephalopathy or brain dysfunction, altered MS, confusion, delirium, coma**  **V: vitals, unstable -- tachycardia, labile BP, cause diaphoresis**  **E: enzymes (such as elevated creatine kinase in blood, myoglobinuremia.**  **enzymes are normally found inside skeletal muscle cells, so finding them around in blood or urine typically indicates rhabdomyolysis or abnormal skeletal muscle breakdown. These enzymes can be harmful to the kidneys and often lead to acute renal failure.**  **R: rigidity of muscles, an increased muscle tone that causes constant resistance when another person tries to move the joint of the affected individual. may be referred to as "lead pipe" rigidity.**    Compared to serotonin syndrome: neuroleptic malignant syndrome tends to [cause more severe hyperthermia and muscle rigidity. In addition, individuals with serotonin syndrome typically also experience mydriasis, hyperreflexia, myoclonus, and diarrhea.]  Treatment of neuroleptic malignant syndrome begins by [discontinuing the causative medication], which can be followed by administration of muscle relaxants like [dantrolene], as well as dopamine agonists like bromocriptine.    **21. Tardive dyskinesia s/s, definition/effects**  Atypical Antipsychotics are associated with a lower incidence of movement disorders compared to First generation antipsychotics. But they still occur to a greater degree than what is preferred. All FGA can cause TD.   Involuntary movements of the tongue, lips, face, trunk, and extremities occur in patients with long-term exposure to antipsychotics. Super sensitivity of D2 receptors after long-term exposure to AP, resulting in downregulation of D2 receptors.  AIMS is used to quantify severity of TD and should be considered as a regular and routine part of clinical management.       **22. Metabolic syndrome: what is it, monitoring, meds**  SGA have increased risk of causing weight gain, dyslipidemia, diabetes.  The risk factors include elevated blood glucose, elevated triglycerides, large waist circumference, hypertension, and decreased HDL cholesterol.^1^ Taking antipsychotics can increase an individual's risk of developing metabolic syndrome. This mechanism is due to the ability of antipsychotic medications to cause weight gain by blocking the H1 histamine receptors and 5HT2C serotonin receptors however, there is another mechanism involving insulin regulation that is not yet fully understood.   Risk of Weight Gain Among Antipsychotics  Low  Moderate  High  ---------------- --------------- ------------- aripiprazole  asenapine  clozapine  brexpiprazole  iloperidone  olanzapine  cariprazine  paliperidone     lumateperone  quetiapine     lurasidone  risperidone     ziprasidone           Weight     BMI     Waist circumference     Blood pressure     Fasting plasma glucose or HbA1C     Lipid profile  When possible, select agents with lower incidences of weight gain and/or dyslipidemia. Or add metformin  **23. Hyperprolactinemia**  - **Breast secretions and 5HT2A antagonism (see notes on tuberoinfundibular slide)**  - **How do you treat hyperprolactinemia**  Breast secretions and 5HT2A antagonism: Treatment= augment with a small dose of Abilify (aripiprazole), a partial agonist  Stimulation of serotonin 2A receptors (agonism) stimulates prolactin release. Since they have opposing effects on prolactin, adding serotonin 2A antagonism to dopamine 2 antagonism results in a neutral effect on prolactin and may relieve breast secretions caused by dopamine 2 antagonism alone.        **24. Which meds come in LAI? When would you recommend an LAI?** Use LAI for patients unable to comply with oral medication, patients who are prone to forgetting to take their meds. Longest acting is Invega Trinza (requires 4 months of Invega Sustenna first). Must do oral trial first before giving a LAI incase patient doesn't tolerate the med  **25. Be able to recognize your typical (1^st^ gen) antipsychotics and know when you would or WOULD NOT use them**  **Low Potency**  **High Potency**  ---------------------------- --------------------------- chlorpromazine (Thorazine  Fluphenazine (Prolixin)      Haloperidol (Haldol)     Loxapine (Loxitane)     Perphenazine (Trilofon)     Pimozide (Orap)  Chlorpromazine- more sedation and anticholinergic effects. Fluphenazine, Haloperidol, and Pimozide have the biggest risk of EPS. All FGA can cause TD   **26. Acetylcholine cognitive decline in schizophrenia**  Impairments, such as difficulties with executive functioning, attention, and memory, are common in schizophrenia and are believed to be related to the downregulation of acetylcholine and disruption of cholinergic receptors  **27. How do VMAT2 inhibitors work?** VMAT2 inhibitors bind to dopamine in the presynaptic neuron thus decreasing dopamine levels in the postsynaptic neuron. Examples are Valbenazine and deutetrabenazine. Used for tardive dyskinesia  **28. What are muscarinic receptors? What do they do? What does that mean? Anticholinergic**  Blockade of H1-histaminic receptors (antihistaminic): sedation and weight gain.  Blockade of M1-muscarinic cholinergic receptors (anticholinergic): Dry mouth, Blurred vision, Urinary retention, Constipation, Drowsiness  Blockade of α-1 adrenergic receptors- Dizziness, Orthostatic hypotension, Drowsiness    Effects on receptors other than dopamine or serotonin are responsible for many side effects of antipsychotic drugs, such as sedation and weight gain (blockade of histamine receptors) as well as postural hypotension (alpha receptor blockade).  **29. Antipsychotics and common side effects**  - **Which are worst for weight gain and metabolic dysfunction-** olanzapine, clozapine  - **Which receptors or pathways are responsible for certain side effects (excess/deficient, neurotransmitter receptors)-** Histamine H1 causes weight gain, sedation. Alpha 1 adrenergic causes hypotension. M1 muscarinic blockade causes anticholinergic effects  - **Which are worse for EPS-** first generation antipsychotics; risperidone, paliperidone    [Clozapine]- not used first line (use for treatment resistant cases). Good for positive and negative symptoms. Cause weight gain. Risk of agranulocytosis. Monitor serial ANCs with REMS registry.   [Aripiprazole]- D2 partial agonist. Cause akathisia. Less weight gain and sedation. Comes in LAI. long half life- good if patient forgets to take med (also cariprazine)  [Brexpiprazole]- D2 partial agonist. Cause akathisia. Less weight gain and sedation. Relative to aripiprazole. Good for depression. May improve cognition. Approved for agitation in alzheimer's. [Risperidone]- potent D2 blocker (EPS). Hyperprolactinemia (add aripiprazole to mitigate). Comes in LAI.   [Paliperidone]- potent D2 blocker (EPS). Hyperprolactinemia. Relative to risperidone. Approved for schizoaffective disorder. Comes in LAI.   [Ziprasidone (Geodon)]- QT prolongation! Less sedating, less weight gain. Do EKG before starting.  [Olanzapine]- weight gain, sedation! Risk of DRESS syndrome (fever, rash, facial swelling, abnormal eosinophils; symptoms occur 2-6 weeks after taking med). Approved for bipolar depression.  [Quetiapine]- sedation, weight gain, metabolic dysfunction. Dose at night. Approved for bipolar depression, depression, mania, and psychosis. Different doses have different effects (mama bear, baby bear dosing) \600 psychosis  [Iloperidone]- can cause hypotension. Start low and titrate slowly. Little EPS or metabolic sx.   [Asenapine]- sublingual. Good med if cheeking is a concern; can be PRN; good for pt with noncompliance if they haven't trialed a med before starting LAI   [Lurasidone]- approved for bipolar depression, NOT mania. Only atypical not to have risk of QT prolongation. Must take with food- taking on empty stomach decreases absorption by 50%.   [Cariprazine (Vraylar)]- D2 and D3 partial agonist. Good for patient who might be forgetful to take med due to long half life. Approved for bipolar depression. Use if patient has mainly negative symptoms  [Lumateperone (Calypta)]- approved for bipolar depression. Pro-social effects, minimal weight gain, metabolic dysfunction, EPS.    **30. Similarities & differences in FGAs & SGAs **  FGA and SGA both block D2, the difference is that SGA also block 5HT2A  Both 1st generation and 2nd generation AP treat positive symptoms. First generation antipsychotics have a higher affinity for D2 receptors. It's like wiping out so much dopamine in the nigrostriatal pathway that movement disorders (EPS) are likely. 2nd generation AP have a lower affinity for D2 receptors and also target 5HT2A - this helps decrease the likelihood of EPS.   Neuroleptic Malignant Syndrome is more likely to occur in 1st generation compared to 2nd generation (can still occur in both though).  Blocking dopamine receptors (specifically D2 receptors) leads to an excess of acetylcholine, contributing to EPS.  **31. Schizophrenia and brain imaging abnormalities**  Enlarged ventricles  Smaller frontal and temporal lobes (reduced symmetry in temporal, frontal, and occipital lobes)  Cortical atrophy  Decreased cerebral blood flow  Hippocampal and amygdala reduction                          **32. Acetylcholine in schizophrenia, EPS, cognition**  Blockade of the D2 receptor in the extrapyramidal system leads to a striatal dopaminergic-cholinergic neurotransmitter imbalance, resulting in extrapyramidal symptoms (EPS). Blockage of dopamine causes excess of acetylcholine which causes EPS. Use anticholinergics (diphenhydramine, benztropine) to decrease acetylcholine.        **33. Clozapine: side effects, issues with it, when to give, lab values**  clozapine is currently the only medication approved for **treatment resistant schizophrenia**. Clozapine - low incidence of extrapyramidal side effects and very few cases of tardive dyskinesia.   Very sedating and has some anticholinergic and antiadrenergic side effects.  Sedation and sialorrhea (drooling) are the most troublesome side effects that often lead to early discontinuation. Clozapine lowers the seizure threshold and can cause hepatitis. The most serious side effect, however, is a severe blood disorder, agranulocytosis, which has caused several deaths in the United States.   These deaths have occurred despite the mandatory weekly monitoring of white blood cell count. (Note: After six months with normal blood counts, monitoring can then take place on a biweekly basis.)