Which of the following neuropharmacological agents is described as a melatonergic antidepressant?
A. Melatonin has not been demonstrated to have clinically significant antidepressant properties. Ropinirole is a dopamine agonist; it acts via the stimulation of postsynaptic dopamine D2 -type receptors within the basal ganglia. Agomelatine is a novel agent promoted as a melatonergic antidepressant; its main antidepressant effect is mediated via 5-HT2C antagonism, which may modulate noradrenergic and dopaminergic neurotransmission. L-tryptophan is a serotonin precursor and is not considered as melatonergic drug. Modafinil is not used as an antidepressant; it acts via an influence on dopamine-dependent adrenergic signalling, though the exact mechanism is still unclear.
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Which of the following medications can be used to treat narcolepsy and associated sleep disorders?
D. Buprenorphine and naloxone act via opioid receptors; they are not indicated in sleep disorders such as narcolepsy. Antidepressants, including fluoxetine and tricyclics such as imipramine, can help cataplexy (sudden loss of muscle tone) in narcolepsy. Modafinil is a drug with stimulant properties and it is used to promote wakefulness in narcolepsy and allied disorders.
Which of the following drugs has some evidence for the treatment of resistant depression as an augmenting agent to SSRIs?
D. Pindolol acts as a partial agonist at 5-HT1A receptors. Several controlled studies in the past have shown that the addition of pindolol to SSRI therapy rapidly potentiates the effects of these antidepressants. However, despite the rapidity of improvement with the combination, most studies found no overall advantage at the end of the study period. Systematic review of randomized controlled trials does not support the use of pindolol and β-blockers are not licensed for the treatment of depression. Pentazocine is a partial agonist at kappa opiate receptors; it has some psychotomimetic properties but is not used as an antidepressant. In fact, it may induce depression. Tramadol is an opioid analgesic with no antidepressant effects.
The half-life of atomoxetine in most individuals is:
E. The mean elimination half-life of atomoxetine after oral administration is 5.2 hours. In poor metabolizers (CYP2D6 polymorphism) the mean elimination half-life is more than 20 hours, due to reduced clearance. Nearly 80% of atomoxetine is excreted in the urine. Atomoxetine does not affect the cytochrome P450 2D6 enzyme system. The effects of atomoxetine last longer than would be expected from its half-life; hence, once-daily administration is effective.
Which of the following is considered to be the safest of all MAO-A inhibitors when used in combination with other antidepressants to treat depression?
C. Antidepressant combinations involving MAOIs require close monitoring due to the risk of serotonergic and hypertensive side-effects. Phenelzine is supposed to be the safest MAO-A inhibitor in combination therapy for depression. It is a derivative of hydrazine similar to isonaizid, but the latter is mainly used as an antituberculosis drug and has only a weak antidepressant action. Selegeline is an MAO-B inhibitor.
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