Rls and comorbidity

Health-related quality of life is substantially reduced in RLS patients and is comparable to other chronic neurological disorders such as Parkinson’s disease and stroke

Severity of RLS plus MDD symptoms have the most significant negative impact on quality of life

RLS is also common in those who are pregnant, suffer from renal disease, or rheumatoid arthritis

Rls treatment

Dopaminergic drugs are the first-line treatment and have been shown to relieve symptoms in 70%–90% of patients

Ropinirole (Requip) and pramipexole (Mirapex) are approved agents that are D2 receptor agonists

Adverse effects include induction of compulsive behaviors, nausea, asthenia, sedation, somnolence, syncope, hallucinations, or dyskinesias

Oral iron treatment may significantly reduce RLS severity

Opioids may be considered for patients presenting with neuropathy or painful dysthesias

Alpha-2-delta calcium channel blocking anticonvulsants (gabapentin [Neurontin] or pregabalin [Lyrica]) have also been studied, showing RLS symptom reduction

Posttest self-assessment question and answer

Which of the following hypnotic agents is less likely to be addictive, impair psychomotor function, or cause respiratory suppression?

A. Ramelteon (Rozerem)

B. Zolpidem (Ambien)

C. Doxepin (Silenor)

D. Temazepam (Restoril)

E. A and C

F. B and D

G. None of the above

Answer: E

Ramelteon and doxepin are not GABA-A receptor positive allosteric modulators (PAMs), are therefore not related to the true BZ or BZRA class of hypnotics, are not associated with addiction, and appear to have little to no respiratory suppression or psychomotor impairment, comparatively speaking.

References

1.Salas RE, Gamaldo CE, Allen RP. Update in restless legs syndrome. Curr Opin Neurol 2010; 23:401–6.

2.Klerman GL, Weissman M, Rounsville BJ, Chevron ES. Interpersonal Psychotherapy of Depression. New York, NY: Basic Books Inc., 1984; pp. 14–16.

3.Stahl SM. Stahl’s Essential Psychopharmacology, 4th edn. New York, NY: Cambridge University Press, 2013.

4.Stahl SM. Stahl’s Essential Psychopharmacology: The Prescriber’s Guide, 5th edn. New York, NY: Cambridge University Press, 2014.

5.Zarate CA Jr., Payne JL, Singh J, et al. Pramipexole for bipolar II depression: a placebo-controlled proof of concept study. Biol Psychiatry 2004; 56:54–60.

6.Walsh JK, Zammit G, Schweitzer PK, Ondrasik J, Roth T. Tiagabine enhances slow wave sleep and sleep maintenance in primary insomnia. Sleep Med 2006; 7:155–61.

7.Emens J, Lewy A, Kinzie JM, Arntz D, Rough J. Circadian misalignment in major depressive disorder. Psychiatry Res 2009; 168:259–61.

8.Lewy AJ. The dim light melatonin onset, melatonin assays and biological rhythm research in humans. Biol Signals Recept 1999; 8:79–83.

9.Aimone JB, Deng W, Gage FH. Adult neurogenesis: integrating theories and separating functions. Trends Cogn Sci 2010; 14:325–37.

10.Holmes MM, Galea LA, Mistlberger RE, Kempermann G. Adult hippocampal neurogenesis and voluntary running activity: circadian and dose-dependent effects. J Neurosci Res 2004; 76:216–22.

11.Molteni R, Calabrese F, Pisoni S, et al. Synergistic mechanisms in the modulation of the neurotrophin BDNF in the rat prefrontal cortex following acute agomelatine administration. World J Biol Psychiatry 2010; 11:148–53.

12.Armstrong SM, McNulty OM, Guardiola-Lemaitre B, Redman JR. Successful use of S20098 and melatonin in an animal model of delayed sleep-phase syndrome (DSPS). Pharmacol Biochem Behav 1993; 46:45–9.

13.Millan MJ, Gobert A, Lejeune F, et al. The novel melatonin agonist agomelatine (S20098) is an antagonist at 5-hydroxytryptamine2C receptors, blockade of which enhances the activity of frontocortical dopaminergic and adrenergic pathways. J Pharmacol Exp Ther 2003; 306:954–64.

14.Katona C, Hansen T, Olsen CK. A randomized, double-blind, placebo-controlled, duloxetine-referenced, fixed-dose study comparing the efficacy and safety of Lu AA21004 in elderly patients with major depressive disorder. Intern Clin Psychopharmacol 2012; 27:215–23.

Patient file

The Case:

The patient who interacted with everything

The Question:

What to do when treating depression is thwarted by pharmacokinetic problems and side effects

The Dilemma:

CYP450 enzyme genetic alterations may cause subtherapeutic, side effect-prone treatment

Pretest self-assessment question (answer at the end of the case)

Which of the following medications is often used in regulatory trials to determine if a CYP450 inhibition interaction exists with an experimental drug?

A. Temazepam (Restoril)

B. Desipramine (Norpramin)

C. Desvenlafaxine (Pristiq)

D. Paliperidone (Invega)