Pregnancy

• Risk Category C [some animal studies show adverse effects; no controlled studies in humans]

• Not generally recommended for use during pregnancy, especially during first trimester

• Nonetheless, continuous treatment during pregnancy may be necessary and has not been proven to be harmful to the fetus

• Must weigh the risk of treatment (first trimester fetal development, third trimester newborn delivery) to the child against the risk of no treatment (recurrence of depression, maternal health, infant bonding) to the mother and child

• For many patients this may mean continuing treatment during pregnancy

• Neonates exposed to SSRIs or SNRIs late in the third trimester have developed complications requiring prolonged hospitalization, respiratory support, and tube feeding; reported symptoms are consistent with either a direct toxic effect of SSRIs and SNRIs or, possibly, a drug discontinuation syndrome, and include respiratory distress, cyanosis, apnea, seizures, temperature instability, feeding difficulty, vomiting, hypoglycemia, hypotonia, hypertonia, hyperreflexia, tremor, jitteriness, irritability, and constant crying

Breast Feeding

• Some drug is found in mother’s breast milk

• Trace amounts may be present in nursing children whose mothers are on venlafaxine

• If child becomes irritable or sedated, breast feeding or drug may need to be discontinued

• Immediate postpartum period is a high-risk time for depression, especially in women who have had prior depressive episodes, so drug may need to be reinstituted late in the third trimester or shortly after childbirth to prevent a recurrence during the postpartum period

• Must weigh benefits of breast feeding with risks and benefits of antidepressant treatment versus nontreatment to both the infant and the mother

• For many patients, this may mean continuing treatment during breast feeding

VENLAFAXINE: THE ART OF PSYCHOPHARMACOLOGY

Potential Advantages

• Patients with retarded depression

• Patients with atypical depression

• Patients with comorbid anxiety

• Patients with depression may have higher remission rates on SNRIs than on SSRIs

• Depressed patients with somatic symptoms, fatigue, and pain

• Patients who do not respond or remit on treatment with SSRIs

Potential Disadvantages

• Patients sensitive to nausea

• Patients with borderline or uncontrolled hypertension

• Patients with cardiac disease

Primary Target Symptoms

• Depressed mood

• Energy, motivation, and interest

• Sleep disturbance

• Anxiety

Pearls

✽ May be effective in patients who fail to respond to SSRIs, and may be one of the preferred treatments for treatment-resistant depression

✽ May be used in combination with other antidepressants for treatment-refractory cases

• XR formulation improves tolerability, reduces nausea, and requires only once daily dosing

• May be effective in a broad array of anxiety disorders

• May be effective in adult ADHD

• Not studied in stress urinary incontinence

✽ Has greater potency for serotonin reuptake blockade than for norepinephrine reuptake blockade, but this is of unclear clinical significance as a differentiating feature from other SNRIs

✽ In vitro binding studies tend to underestimate in vivo potency for reuptake blockade, as they do not factor in the presence of high concentrations of an active metabolite, higher oral mg dosing, or the lower protein binding which can increase functional drug levels at receptor sites

• Effective dose range is broad (i.e., 75–375 mg in many difficult cases, and up to 600 mg or more in heroic cases)

✽ Preliminary studies in neuropathic pain and fibromyalgia suggest potential efficacy

• Efficacy as well as side effects (especially nausea and increased blood pressure) are dose-dependent

• Blood pressure increases rare for XR formulation in doses up to 225 mg

• More withdrawal reactions reported upon discontinuation than for some other antidepressants

• May be helpful for hot flushes in perimenopausal women

• May be associated with higher depression remission rates than SSRIs

✽ Because of recent studies from the U.K. that suggest a higher rate of deaths from overdose with venlafaxine than with SSRIs, and because of its potential to affect heart function, venlafaxine can only be prescribed in the U.K. by specialist doctors and is contraindicated there in patients with heart disease

• Overdose data are from fatal toxicity index studies, which do not take into account patient characteristics or whether drug use was first- or second-line

• Venlafaxine’s toxicity in overdose is less than that for tricyclic antidepressants

Suggested Reading

Buckley NA, McManus PR, Fatal toxicity of serotonergic and other antidepressant drugs: analysis of United Kingdom mortality data. BMJ 2002;325:1332–3.

Cheeta S, Schifano F, Oyefeso A, Webb L, Ghodse AH. Antidepressant-related deaths and antidepressant prescriptions in England and Wales, 1998–2000. Br J Psychiatry 2004;184:41–7.

Davidson J, Watkins L, Owens M, Krulewicz S, Connor K, Carpenter D, et al. Effects of paroxetine and venlafaxine XR on heart rate variability in depression. J Clin Psychopharmacol 2005;25:480–4.

Hackett D. Venlafaxine XR in the treatment of anxiety. Acta Psychiatrica Scand 2000;406(Suppl):S30–35.

Sheehan DV. Attaining remission in generalized anxiety disorder: venlafaxine extended-release comparative data. J Clin Psychiatry 2001;62 (Suppl 19):S26–31.

Smith D, Dempster C, Glanville J, Freemantle N, Anderson I. Efficacy and tolerability of venlafaxine compared with selective serotonin reuptake inhibitors and other antidepressants: a meta-analysis. Br J Psychiatry 2002;180:396–404.

Wellington K, Perry CM. Venlafaxine extended-release: a review of its use in the management of major depression. CNS Drugs 2001;15:643–69.

VILAZODONE

VILAZODONE: THERAPEUTICS

Brands

• Viibryd

see index for additional brand names

Generic?

No

Class

• SPARI (serotonin partial agonist reuptake inhibitor)

• Dual-acting serotonin reuptake inhibitor plus 5HT1A partial agonist

Commonly Prescribed for

(bold for FDA approved)

• Major depressive disorder

• Anxiety

• Obsessive compulsive disorder

How the Drug Works

• Boosts neurotransmitter serotonin

• Blocks serotonin reuptake pump (serotonin transporter)

• Desensitizes serotonin receptors, especially serotonin 1A autoreceptors

• Presumably increases serotonergic neurotransmission

• Partial agonist actions at presynaptic somatodendritic serotonin 1A autoreceptors may theoretically enhance serotonergic activity and contribute to antidepressant actions

• Partial agonist actions at postsynaptic serotonin 1A receptors may theoretically diminish sexual dysfunction caused by serotonin reuptake inhibition