Breast Feeding

• Unknown if agomelatine is secreted in human breast milk, but all psychotropics assumed to be secreted in breast milk

• Therefore, breast feeding or drug needs 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

AGOMELATINE: THE ART OF PSYCHOPHARMACOLOGY

Potential Advantages

• Patients with lack of energy, anhedonia, anxious comorbidity, and sleep-wake disturbances

• Patients particularly concerned about sexual side effects or weight gain

Potential Disadvantages

• Patients with hepatic impairment

Primary Target Symptoms

• Depressed mood, anhedonia

• Daytime functioning

Pearls

• Agomelatine represents a novel approach to depression through a novel pharmacologic profile, agonist at melatonergic MT1 / MT2 receptors and antagonist at 5HT2C receptors acting synergistically

• This synergy provides agomelatine with a distinctive efficacy profile, different from conventional antidepressants with potentially an early and continuous improvement over time

• Agomelatine improves anhedonia early in treatment

• Agomelatine may improve sleep quality by promoting proper maintenance of circadian rhythms underlying a normal sleep-wake cycle

Suggested Reading

DeBodinat C, Guardiola-Lemaitre B, Mocaer E, et al. Agomelatine, the first melatonergic antidepressant: discovery, characterization, and development. Nat Rev Drug Discov 2010;9:628–42.

Demyttenaere K, Corruble E, Hale A, et al. A pooled analysis of six month comparative efficacy and tolerability in four randomized clinical trials: agomelatine versus escitalopram, fluoxetine, and sertraline. CNS Spectr 2013;18:163–70.

Goodwin GM, Emsley R, Rembry S, Rouillon F. Agomelatine prevents relapse in patients with major depressive disorder without evidence of a discontinuation syndrome: a 24-week randomized, double-blind, placebo-controlled trial. J Clin Psychiatry 2009;70:1128–37.

Kasper S, Corruble E, Hale A, et al. Antidepressant efficacy of agomelatine versus SSRI/SNRI: results from a pooled analysis of head-to-head studies without a placebo control. Int Clin Psychopharmacol 2013;28(1):12–19.

Martinotti G, Sepede G, Gambi F, et al. Agomelatine versus venlafaxine XR in the treatment of anhedonia in major depressive disorder: a pilot study. J Clin Psychopharmacol 2012;32(4):487–91.

Racagni G, Riva MA, Molteni R, et al. Mode of action of agomelatine: synergy between melatonergic and 5-HT2C receptors. World J Biol Psychiatry 2011;12(8):574–87.

Stahl SM, Fava M, Trivedi M, Caputo A, Shah A, Post A. Agomelatine in the treatment of major depressive disorder. An 8 week, multicenter, randomized, placebo-controlled trial. J Clin Psychiatry 2010;71(5):616–26.

Stein DJ, Picarel-Blanchot F, Kennedy SH. Efficacy of the novel antidepressant agomelatine on anxiety symptoms in major depression. Hum Psychopharmacol 2013;28(2):151–9.

ALPRAZOLAM

ALPRAZOLAM: THERAPEUTICS

Brands

• Xanax, Xanax XR

see index for additional brand names

Generic?

Yes

Class

• Benzodiazepine (anxiolytic)

Commonly Prescribed for

(bold for FDA approved)

• Generalized anxiety disorder (IR)

• Panic disorder (IR and XR)

• Other anxiety disorders

• Anxiety associated with depression

• Premenstrual dysphoric disorder

• Irritable bowel syndrome and other somatic symptoms associated with anxiety disorders

• Insomnia

• Acute mania (adjunctive)

• Acute psychosis (adjunctive)

• Catatonia

How the Drug Works

• Binds to benzodiazepine receptors at the GABA-A ligand-gated chloride channel complex

• Enhances the inhibitory effects of GABA

• Boosts chloride conductance through GABA-regulated channels

• Inhibits neuronal activity presumably in amygdala-centered fear circuits to provide therapeutic benefits in anxiety disorders

How Long Until It Works

• Some immediate relief with first dosing is common; can take several weeks with daily dosing for maximal therapeutic benefit

If It Works

• For short-term symptoms of anxiety – after a few weeks, discontinue use or use on an “as-needed” basis

• For chronic anxiety disorders, the goal of treatment is complete remission of symptoms as well as prevention of future relapses

• For chronic anxiety disorders, treatment most often reduces or even eliminates symptoms, but not a cure since symptoms can recur after medicine stopped

• For long-term symptoms of anxiety, consider switching to an SSRI or SNRI for long-term maintenance

• If long-term maintenance with a benzodiazepine is necessary, continue treatment for 6 months after symptoms resolve, and then taper dose slowly

• If symptoms reemerge, consider treatment with an SSRI or SNRI, or consider restarting the benzodiazepine; sometimes benzodiazepines have to be used in combination with SSRIs or SNRIs for best results