Breast Feeding

• Some drug is found in mother’s breast milk

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

• 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

FLUVOXAMINE: THE ART OF PSYCHOPHARMACOLOGY

Potential Advantages

• Patients with mixed anxiety/depression

• Generic is less expensive than brand name where available

Potential Disadvantages

• Patients with irritable bowel or multiple gastrointestinal complaints

• Can require dose titration and twice daily dosing

Primary Target Symptoms

• Depressed mood

• Anxiety

Pearls

✽ Often a preferred treatment of anxious depression as well as major depressive disorder comorbid with anxiety disorders

• Some withdrawal effects, especially gastrointestinal effects

• May have lower incidence of sexual dysfunction than other SSRIs

• Preliminary research suggests that fluvoxamine is efficacious in obsessive-compulsive symptoms in schizophrenia when combined with antipsychotics

• Not FDA approved for depression, but used widely for depression in many countries

• CR formulation may be better tolerated than immediate-release formulation, particularly with less sedation

• SSRIs may be less effective in women over 50, especially if they are not taking estrogen

• SSRIs may be useful for hot flushes in perimenopausal women

✽ Actions at sigma 1 receptors may explain in part fluvoxamine’s sometimes rapid onset effects in anxiety disorders and insomnia

✽ Actions at sigma 1 receptors may explain potential advantages of fluvoxamine for psychotic depression and delusional depression

✽ For treatment-resistant OCD, consider cautious combination of fluvoxamine and clomipramine by an expert

• Normally, clomipramine (CMI), a potent serotonin reuptake blocker, at steady state is metabolized extensively to its active metabolite desmethyl-clomipramine (de-CMI), a potent noradrenergic reuptake blocker

• Thus, at steady state, plasma drug activity is generally more noradrenergic (with higher de-CMI levels) than serotonergic (with lower parent CMI levels)

• Addition of a CYP450 1A2 inhibitor, fluvoxamine, blocks this conversion and results in higher CMI levels than de-CMI levels

• Thus, addition of the SSRI fluvoxamine to CMI in treatment-resistant OCD can powerfully enhance serotonergic activity, not only due to the inherent serotonergic activity of fluvoxamine, but also due to a favorable pharmacokinetic interaction inhibiting CYP450 1A2 and thus converting CMI’s metabolism to a more powerful serotonergic portfolio of parent drug

Suggested Reading

Cheer SM, Figgitt DP. Spotlight on fluvoxamine in anxiety disorders in children and adolescents. CNS Drugs 2002;16:139–44.

Edwards JG, Anderson I. Systematic review and guide to selection of selective serotonin reuptake inhibitors. Drugs 1999;57:507–33.

Figgitt DP, McClellan KJ. Fluvoxamine. An updated review of its use in the management of adults with anxiety disorders. Drugs 2000;60:925–54.

Omori M, Watanabe N, Nakagawa A, et al. Fluvoxamine versus other anti-depressive agents for depression. Cochrane Database Syst Rev 2010;17(3):CD006114.

Pigott TA, Seay SM. A review of the efficacy of selective serotonin reuptake inhibitors in obsessive-compulsive disorder. J Clin Psychiatry 1999;60:101–6.

GABAPENTIN

GABAPENTIN: THERAPEUTICS

Brands

• Neurontin

• Horizant

see index for additional brand names

Generic?

Yes (not for extended release)

Class

• Anticonvulsant, antineuralgic for chronic pain, alpha 2 delta ligand at voltage-sensitive calcium channels

Commonly Prescribed for

(bold for FDA approved)

• Partial seizures with or without secondary generalization (adjunctive)

• Postherpetic neuralgia

• Restless leg syndrome (extended release)

• Neuropathic pain/chronic pain

• Anxiety (adjunctive)

• Bipolar disorder (adjunctive)

How the Drug Works

• Is a leucine analogue and is transported both into the blood from the gut and also across the blood-brain barrier into the brain from the blood by the system L transport system

✽ Binds to the alpha 2 delta subunit of voltage-sensitive calcium channels

• This closes N and P/Q presynaptic calcium channels, diminishing excessive neuronal activity and neurotransmitter release

• Although structurally related to gamma-aminobutyric acid (GABA), no known direct actions on GABA or its receptors