THERAPEUTICS

Brands

• Effexor
• Effexor XR
• see index for additional brand names

Generic?

• Yes

Class

• SNRI (dual serotonin and norepinephrine reuptake inhibitor); often classified as an antidepressant, but it is not just an antidepressant

Commonly Prescribed for

• (bold for FDA approved)
• Depression
• Generalized anxiety disorder (GAD)
• Social anxiety disorder (social phobia)
• Panic disorder
• Posttraumatic stress disorder (PTSD)
• Premenstrual dysphoric disorder (PMDD)

How the Drug Works

• Boosts neurotransmitters serotonin, norepinephrine/noradrenaline, and dopamine
• Blocks serotonin reuptake pump (serotonin transporter), presumably increasing serotonergic neurotransmission
• Blocks norepinephrine reuptake pump (norepinephrine transporter), presumably increasing noradrenergic neurotransmission
• Presumably desensitizes both serotonin 1A receptors and beta adrenergic receptors
• Since dopamine is inactivated by norepinephrine reuptake in frontal cortex, which largely lacks dopamine transporters, venlafaxine can increase dopamine neurotransmission in this part of the brain
• Weakly blocks dopamine reuptake pump (dopamine transporter), and may increase dopamine neurotransmission

How Long Until It Works

• Onset of therapeutic actions usually not immediate, but often delayed 2-4 weeks
• If it is not working within 6-8 weeks for depression, it may require a dosage increase or it may not work at all
• By contrast, for generalized anxiety, onset of response and increases in remission rates may still occur after 8 weeks, and for up to 6 months after initiating dosing
• May continue to work for many years to prevent relapse of symptoms

If It Works

• The goal of treatment is complete remission of current symptoms as well as prevention of future relapses
• Treatment most often reduces or even eliminates symptoms, but not a cure since symptoms can recur after medicine stopped
• Continue treatment until all symptoms are gone (remission), especially in depression and whenever possible in anxiety disorders
• Once symptoms gone, continue treating for 1 year for the first episode of depression
• For second and subsequent episodes of depression, treatment may need to be indefinite
• Use in anxiety disorders may also need to be indefinite

If It Doesn’t Work

• Many patients only have a partial response where some symptoms are improved but others persist (especially insomnia, fatigue, and problems concentrating)
• Other patients may be nonresponders, sometimes called treatment-resistant or treatment-refractory
• Some patients who have an initial response may relapse even though they continue treatment, sometimes called “poop-out”
• Consider increasing dose, switching to another agent or adding an appropriate augmenting agent
• Consider psychotherapy
• Consider evaluation for another diagnosis or for a comorbid condition (e.g., medical illness, substance abuse, etc.)
• Some patients may experience apparent lack of consistent efficacy due to activation of latent or underlying bipolar disorder, and require antidepressant discontinuation and a switch to a mood stabilizer

Best Augmenting Combos for Partial Response or Treatment Resistance

• Mirtazapine (“California rocket fuel”; a potentially powerful dual serotonin and norepinephrine combination, but observe for activation of bipolar disorder and suicidal ideation)
• Bupropion, reboxetine, nortriptyline, desipramine, maprotiline, atomoxetine (all potentially powerful enhancers of noradrenergic action, but observe for activation of bipolar disorder and suicidal ideation)
• Modafinil, especially for fatigue, sleepiness, and lack of concentration
• Mood stabilizers or atypical antipsychotics for bipolar depression, psychotic depression or treatment-resistant depression
• Benzodiazepines
• If all else fails for anxiety disorders, consider gabapentin or tiagabine
• Hypnotics or trazodone for insomnia
• Classically, lithium, buspirone, or thyroid hormone

Tests

• Check blood pressure before initiating treatment and regularly during treatment