<style> .reveal h1, .reveal h2, .reveal h3, .reveal h4, .reveal h5, .reveal h6 { font-family: Arial; font-weight:bold; } .reveal .slides { text-align: left; padding-right:50px; font-size: 50px; } </style> # Antidepressant Agents --- Presenter: R2林協霆 Supervisor: 王詠醫師 --- Category | Medication --- | --- Selective Serotonin Reuptake Inhibitors | Escitalopram, Sertraline Serotonin Norepinephrine Reuptake Inhibitors | Duloxetine, Venlafaxine Tricyclic | Amitriptyline, Amitriptyline Triazolopyridine | Trazodone Other 5-HT Receptor Modulators | Vortioxetine Tetracyclic | Mirtazapine Aminoketone | Bupropion ---  --- ### Choosing an antidepressant * anticipated adverse events * potential interactions * the person's perception of the efficacy and tolerability of any antidepressants they have previously taken. --- ### Normally choose an SSRI > Take the following into account: * increased risk of ==bleeding==. Consider prescribing a gastroprotective drug in older people who are taking s or aspirin. * Fluoxetine, fluvoxamine and paroxetine have a higher propensity for drug interactions. * For people who also have a chronic physical health problem, consider using ==citalopram== or ==sertraline== as these have a lower propensity for interactions. * Paroxetine is associated with a higher incidence of discontinuation symptoms. --- ### toxicity in overdose for people at significant risk of suicide * venlafaxine is associated with a greater risk of death from overdose * the greatest risk in overdose is with TCAs, except for lofepramine. --- ### additional considerations * Do not prescribe subtherapeutic doses of antidepressants. --- ### Monitoring * For people who are not considered to be at increased risk of suicide, normally see them after 2 weeks * ==If a person experiences side effects early in treatment== * monitoring symptoms closely * stopping or changing to a different antidepressant * short-term concomitant treatment * benzodiazepine if anxiety --- ### Initial lack of response * If response is absent or minimal after 3 to 4 weeks of treatment with a therapeutic dose * increasing the dose or switching * If there is some improvement by 4 weeks, continue treatment for another 2 to 4 weeks. Consider switching antidepressants if: * response is still not adequate, side effect --- ### Phases of treatment for major depression  --- ### Switching and combining antidepressants * initially, a different SSRl or a better-tolerated newer-generation antidepressant * subsequently, an antidepressant of a different class that may be less well tolerated (such as venlafaxine, a TCA or an MAOI). --- ### Do not normally combine antidepressants in primary care without consulting a consultant psychiatrist --- ### Do not routinely augment an antidepressant with: * a benzodiazepine for more than 2 weeks as there is a risk of dependence * buspirone, carbamazepine, lamotrigine or valproate as there is insufficient evidence for their use --- #### Advise people that if they stop taking antidepressant medication abruptly, miss doses or do not take a full dose, they may have discontinuation symptoms such as: * restlessness * problems sleeping * unsteadiness * sweating * abdominal symptoms * altered sensations (for example electric shock sensations in the head) * altered feelings (for example irritability, anxiety or confusion). ---  ---  --- ### Interactions of SSRIs with other medications Medication | Recommended antidepressant(s) --- | --- NSAIDs | * Do not normally offer SSRIs <br>* Consider mianserin, mirtazapine, moclobemide, reboxetine or trazodone Warfarin or heparin | * Do not normally offer SSRIs <br> * Consider mirtazapine Aspirin | Use SSRIs with caution <br> Consider trazodone/mirtazapine Triptan for Migraine | * Do not offer SSRIs <br> Offer mirtazapine, trazodone, mianserin or reboxetine Theophylline, clozapine, methadone or tizamidine | * Do not normally offer fluvoxamine <br> * Offer sertraline or citalopram --- ### SELECTIVE SEROTONIN REUPTAKE INHIBITORS (SSRIs) #### Sertralin (Zoloft) * ==Depression & OCD (obsessive compulsive disorder)==: 50 mg qd, increase at intervals of ≧1wk, max. 200 mg/day. * ==Panic disorder, social phobia, posttraumatic stress disorder==: 25 mg qd initially, max. 200 mg/day. * ==Premenstrual dysphoric disorder==: 50 mg/day; max.150 mg/day. * ==Generalized anxiety disorder (GAD)== off-label use): Initial, 25 mg qd for 1 week; increase based on response and tolerability. Max: 200 mg/day --- #### Escitalopram 10mg (Lexapro) * Adults: Major depression, Generalized anxiety disorder: Initially, 10 mg qd; may increase to 20 mg/day if needed after≧1wk. * Geriatric patients: 10 mg qd. * More CYP interatcion than Sertralin --- ## Note * Half-lives from 15–75 h * oral activity * Toxicity: Well tolerated but cause sexual dysfunction risk of serotonin syndrome with MAOIs * Interactions: Some CYP inhibition (fluoxetine 2D6, 3A4; fluvoxamine 1A2; paroxetine 2D6) ---  --- Escitalopram | Sertraline ---|---  |  --- ## SEROTONIN-NOREPINEPHRINE REUPTAKE INHIBITORS (SNRIs) ### Duloxetine 30mg  > CrCl < 30 mL/min: Avoid use --- ### Venlafaxine 75mg * PO with food (to minimize GI intolerance). * ==Depression, generalized anxiety disorder==: 75 mg qd initially, increased by 75 mg/day at intervals of≧4 days; max. 225 mg/day (3#). * ==Panic disorder, with or without agoraphobia==: 75 mg qd; increased by 75 mg/day at weekly intervals, max. 225 mg/day. * Dosage in renal impairment: Clcr 10-70 mL/min, 50-75% dose. * Dosage in moderate hepatic impairment: 50% dose. --- ### Note * Toxicity: Anticholinergic, sedation, hypertension (venlafaxine) * Interactions: Some CYP2D6 inhibition (duloxetine, desvenlafaxine) * CYP3A4 interactions with levomilnacipran ---   --- ## TRICYCLIC ANTIDEPRESSANTS (TCAs) * Long half-lives * CYP substrates * active metabolites * Toxicity: Anticholinergic, α-blocking effects, sedation, weight gain, arrhythmias, and seizures in overdose * Interactions: CYP inducers and inhibitors --- ### Imipramine HCl * Depression: Adults, * Inpatients,100 mg/day in divided doses; max. 300 mg/day; * Outpatients,75 mg/day; max. 200 mg/day; maintenance, 50-150 mg/day. * Geriatric patients: Initially, 30-40 mg/day; rarely exceeds 100 mg/day. * Nocturnal enuresis: * 6-12yr: Initially, 25 mg 1hr before bedtime; max. 50 mg. * ＞12yr: Initailly, 25 mg 1hr before bedtime; max. 75 mg. * Early night bedwetters: 25 mg mid-afternoon & hs. ---   --- ## 5-HT RECEPTOR MODULATORS ### Trazodone * Relatively short half-lives * active metabolites * Toxicity: Modest α- and H 1 -receptor blockade (trazodone) * Interactions: Nefazodone inhibits CYP3A4 * 50 mg tid initially; increased by 50 mg/day q3-4d; max. 400 mg/day (outpatients) or 600 mg/day (inpatients). --- ### Vortioxetine 10mg * Extensively metabolized via CYP2D6 and glucuronic acid conjugation * Toxicity: GI disturbances, sexual dysfunction * Interactions: Additive with serotonergic agents * Initial: 5-10 mg QD; * target dose of 20 mg QD (max dose: 20 mg/day) --- ## TETRACYCLICS, UNICYCLIC * Extensive metabolism in liver * Toxicity: Lowers seizure threshold (amoxapine, bupropion); sedation and weight gain (mirtazapine) * Interactions: CYP2D6 inhibitor (bupropion) --- ### Mirtazapine 15mg (Remeron) * 15 mg/day at bedtime, may increase in dose every 1-2 wks to max. 45 mg/day --- ### Bupropion 150mg * Major depression: Initial, 150 mg qd in the morning for 3 days, may increase to 300 mg qd (Max. 300 mg/dose (仿單)) * Max. 150mg qod in severe hepatic cirrhosis. ---   --- ## MONOAMINE OXIDASE INHIBITORS (MAOIs) * Very slow elimination * Toxicity: Hypotension, insomnia * Interactions: Hypertensive crisis with tyramine, other indirect sympathomimetics * serotonin syndrome with serotonergic agents, meperidine --- ### Take Home Message * start from SSRI e.g. Escitalopram 10mg, Sertralin and Citalopram for old people (CYP), * watch out bleeding risk, avoid SSRI with Linezolid * 2 weeks for drug to take effect * if relapse, switch to other SSRI, not combine two drug without psy referral * common alterantives: Trazodone, Mirtazapine, Bupropion * CrCl < 30 mL/min: Avoid use Duloxetine * Imipramine (TCA) can treat nocturnal enuresis