VENLAFAXINE - neiglobal.com

1 VENLAFAXINE . THERAPEUTICS By contrast, for generalized anxiety, onset of response and increases in remission Brands Effexor rates may still occur after 8 weeks, and for Effexor XR up to 6 months after initiating dosing see index for additional brand names May continue to work for many years to Generic? Yes prevent relapse of symptoms If It Works The goal of treatment is complete Class remission of current symptoms as well as Neuroscience-based Nomenclature: prevention of future relapses Serotonin and norepinephrine reuptake Treatment most often reduces or even inhibitor (SN-RI) eliminates symptoms, but not a cure SNRI (dual serotonin and norepinephrine since symptoms can recur after medicine reuptake inhibitor); often classi ed as stopped an antidepressant, but it is not just an Continue treatment until all symptoms are antidepressant gone (remission), especially in depression and whenever possible in anxiety disorders Commonly Prescribed for Once symptoms gone, continue treating for (bold for FDA approved) 1 year for the rst episode of depression Depression For second and subsequent episodes of Generalized anxiety disorder (GAD) depression, treatment may need to be Social anxiety disorder (social phobia) inde nite Panic disorder Use in anxiety disorders may also need to Posttraumatic stress disorder (PTSD) be inde nite Premenstrual dysphoric disorder (PMDD).

2 If It Doesn't Work Many patients have only a partial response where some symptoms are improved but How the Drug Works others persist (especially insomnia, fatigue, Boosts neurotransmitters serotonin, and problems concentrating). norepinephrine/noradrenaline, and dopamine Other patients may be nonresponders, Blocks serotonin reuptake pump (serotonin sometimes called treatment-resistant or transporter), presumably increasing treatment-refractory serotonergic neurotransmission Some patients who have an initial response Blocks norepinephrine reuptake pump may relapse even though they continue (norepinephrine transporter), presumably treatment, sometimes called poop-out . increasing noradrenergic neurotransmission Consider increasing dose, switching to Presumably desensitizes both serotonin 1A another agent or adding an appropriate receptors and beta adrenergic receptors augmenting agent Since dopamine is inactivated by Consider psychotherapy norepinephrine reuptake in frontal cortex, Consider evaluation for another diagnosis which largely lacks dopamine transporters, or for a comorbid condition ( , medical VENLAFAXINE can increase dopamine illness, substance abuse, etc.)

3 Neurotransmission in this part of the brain Some patients may experience apparent Weakly blocks dopamine reuptake pump lack of consistent ef cacy due to activation (dopamine transporter), and may increase of latent or underlying bipolar disorder, and dopamine neurotransmission require antidepressant discontinuation and a switch to a mood stabilizer How Long Until It Works Onset of therapeutic actions usually not Best Augmenting Combos immediate, but often delayed 2 4 weeks for Partial Response or If it is not working within 6 8 weeks Treatment Resistance for depression, it may require a dosage Mirtazapine ( California rocket fuel ; a increase or it may not work at all potentially powerful dual serotonin and 785. VENLAFAXINE (continued). norepinephrine combination, but observe for activation of bipolar disorder and suicidal ideation). Life-Threatening or Bupropion, reboxetine, nortriptyline, Dangerous Side Effects desipramine, maprotiline, atomoxetine Rare seizures (all potentially powerful enhancers of Rare induction of hypomania noradrenergic action, but observe for Rare activation of suicidal ideation and activation of bipolar disorder and suicidal behavior (suicidality) (short-term studies ideation) did not show an increase in the risk of Moda nil, especially for fatigue, sleepiness, suicidality with antidepressants compared and lack of concentration to placebo beyond age 24).

4 Mood stabilizers or atypical antipsychotics for bipolar depression, psychotic Weight Gain depression, or treatment-resistant depression Benzodiazepines Reported but not expected If all else fails for anxiety disorders, Possible weight loss, especially short-term consider gabapentin or tiagabine Hypnotics or trazodone for insomnia Sedation Classically, lithium, buspirone, or thyroid hormone Occurs in signi cant minority Tests May also be activating in some patients Check blood pressure before initiating treatment and regularly during treatment What to Do About Side Effects Wait Wait Wait SIDE EFFECTS Lower the dose In a few weeks, switch or add other drugs How Drug Causes Side Effects Theoretically due to increases in serotonin Best Augmenting Agents for Side and norepinephrine concentrations Effects at receptors in parts of the brain and Often best to try another antidepressant body other than those that cause monotherapy prior to resorting to therapeutic actions ( , unwanted augmentation strategies to treat side actions of serotonin in sleep centers effects causing insomnia, unwanted actions of Trazodone or a hypnotic for insomnia norepinephrine on acetylcholine release Bupropion, sildena l, vardena l, or tadala l causing constipation and dry mouth, etc.)

5 For sexual dysfunction Most side effects are immediate but often Benzodiazepines for jitteriness and anxiety, go away with time especially at initiation of treatment and Notable Side Effects especially for anxious patients Mirtazapine for insomnia, agitation, and Most side effects increase with higher gastrointestinal side effects doses, at least transiently Many side effects are dose-dependent ( , Headache, nervousness, insomnia, they increase as dose increases, or they sedation reemerge until tolerance redevelops). Nausea, diarrhea, decreased appetite Many side effects are time-dependent ( , Sexual dysfunction (abnormal ejaculation/. they start immediately upon dosing and orgasm, impotence). upon each dose increase, but go away with Asthenia, sweating time). SIADH (syndrome of inappropriate Activation and agitation may represent antidiuretic hormone secretion). the induction of a bipolar state, especially Hyponatremia a mixed dysphoric bipolar II condition Dose-dependent increase in blood pressure 786.

6 (continued) VENLAFAXINE . sometimes associated with suicidal VENLAFAXINE has an active metabolite ideation, and require the addition of O-desmethylvenlafaxine (ODV), which is lithium, a mood stabilizer or an atypical formed as the result of CYP450 2D6. antipsychotic, and/or discontinuation of Thus, CYP450 2D6 inhibition reduces the VENLAFAXINE formation of ODV, but this is of uncertain clinical signi cance Consider checking plasma levels of ODV. DOSING AND USE and VENLAFAXINE in nonresponders who tolerate high doses, and if plasma levels Usual Dosage Range are low, experts can prudently prescribe Depression: 75 225 mg/day, once daily doses above 375 mg/day while monitoring (extended-release) or divided into 2 3 closely doses (immediate-release) Do not break or chew VENLAFAXINE XR. GAD: 150 225 mg/day capsules, as this will alter controlled- release properties Dosage Forms For patients with severe problems Capsule (extended-release) mg, discontinuing VENLAFAXINE , dosing may 75 mg, 150 mg need to be tapered over many months Tablet (extended-release) mg, 75 mg, ( , reduce dose by 1% every 3 days 150 mg, 225 mg by crushing tablet and suspending or Tablet 25 mg scored, mg scored, dissolving in 100 mL of fruit juice, and 50 mg scored, 75 mg scored, 100 mg then disposing of 1 mL while drinking the scored rest; 3 7 days later, dispose of 2 mL, and so on).

7 This is both a form of very slow How to Dose biological tapering and a form of behavioral Initial dose mg once daily (extended- desensitization (not for XR). release) or 25 50 mg divided into 2 3 For some patients with severe problems doses (immediate-release) for a week, if discontinuing VENLAFAXINE , it may be tolerated; increase daily dose generally useful to add an SSRI with a long half- no faster than 75 mg every 4 days until life, especially uoxetine, prior to taper of desired ef cacy is reached; maximum dose VENLAFAXINE ; while maintaining uoxetine generally 375 mg/day dosing, rst slowly taper VENLAFAXINE and Usually try doses at 75 mg increments for then taper uoxetine a few weeks prior to incrementing by an Be sure to differentiate between additional 75 mg reemergence of symptoms requiring reinstitution of treatment and withdrawal symptoms Dosing Tips Overdose At all doses, potent serotonin reuptake Can be lethal; may cause no symptoms;. blockade possible symptoms include sedation, 75 225 mg/day may be predominantly convulsions, rapid heartbeat serotonergic in some patients, and dual Fatal toxicity index data from the UK.

8 Serotonin and norepinephrine acting in suggest a higher rate of deaths from other patients overdose with VENLAFAXINE than with SSRIs 225 375 mg/day is dual serotonin and Unknown whether this is related to norepinephrine acting in most patients differences in patients who receive Thus, nonresponders at lower doses VENLAFAXINE or to potential cardiovascular should try higher doses to be assured of toxicity of VENLAFAXINE the bene ts of dual SNRI action At very high doses ( , >375 mg/day), Long-Term Use dopamine reuptake blocked as well in some See doctor regularly to monitor blood patients pressure, especially at doses >225 mg/day Up to 600 mg/day has been given for heroic cases 787. VENLAFAXINE (continued). Habit Forming When treating children, carefully weigh No the risks and bene ts of pharmacological treatment against the risks and bene ts of How to Stop nontreatment with antidepressants and make Taper to avoid withdrawal effects sure to document this in the patient's chart (dizziness, nausea, stomach cramps, Distribute the brochures provided by the sweating, tingling, dysesthesias)

9 FDA and the drug companies Many patients tolerate 50% dose reduction Warn patients and their caregivers about for 3 days, then another 50% reduction for the possibility of activating side effects 3 days, then discontinuation and advise them to report such symptoms If withdrawal symptoms emerge during immediately discontinuation, raise dose to stop Monitor patients for activation of suicidal symptoms and then restart withdrawal ideation, especially children and adolescents much more slowly Withdrawal effects can be more common Do Not Use or more severe with VENLAFAXINE than with If patient has uncontrolled angle-closure some other antidepressants glaucoma If patient is taking an MAOI. Pharmacokinetics If there is a proven allergy to VENLAFAXINE Parent drug has 3 7 hour half-life Active metabolite has 9 13 hour half-life Food does not affect absorption SPECIAL POPULATIONS. Renal Impairment Drug Interactions Lower dose by 25 50%. Tramadol increases the risk of seizures in Patients on dialysis should not receive patients taking an antidepressant subsequent dose until dialysis is completed Can cause a fatal serotonin syndrome.

10 When combined with MAOIs, so do not use Hepatic Impairment with MAOIs or for at least 14 days after Lower dose by 50%. MAOIs are stopped Do not start an MAOI for at least 5 half- Cardiac Impairment lives (5 to 7 days for most drugs) after Drug should be used with caution discontinuing VENLAFAXINE Hypertension should be controlled prior Possible increased risk of bleeding, to initiation of VENLAFAXINE and should be especially when combined with monitored regularly during treatment anticoagulants ( , warfarin, NSAIDs) VENLAFAXINE has a dose-dependent effect on Concomitant use with cimetidine may increasing blood pressure reduce clearance of VENLAFAXINE and raise VENLAFAXINE is contraindicated in patients VENLAFAXINE levels with heart disease in the UK. Could theoretically interfere with the VENLAFAXINE can block cardiac ion channels analgesic actions of codeine or possibly in vitro with other triptans VENLAFAXINE worsens ( , reduces) heart Few known adverse drug interactions rate variability in depression, perhaps due to norepinephrine reuptake inhibition Other Warnings/ Elderly Precautions Some patients may tolerate lower doses Use with caution in patients with history of better seizures Risk of SIADH with SSRIs is higher in the Use with caution in patients with heart elderly disease Reduction in the risk of suicidality with Use with caution in patients with bipolar antidepressants compared to placebo in disorder unless treated with concomitant adults age 65 and older mood-stabilizing agent 788.