Major Depression Disorder: Sleep-Wake Cycle & Antidepressants.

Q: Which of the following changes are seen in REM sleep of depressed patient?

 


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BRAIN STRUCTURES (AND NEUROTRANSMITTERS) IMPLICATED IN SLEEP WAKE CYCLE:

 

  1. Reticularis nucleus (GABA)

  2. Basal forebrain (Acetylcholine)

  3. VLPO: ventrolateral preoptic nucleus (GABA)

  4. Suprachiasmatic nucleus: responsible for wake promoting signals.

  5. Lateral hypothalamus (Orexin)

  6. Tegmentum (Acetylcholine)

  7. TMN: Tuberomammillary nucleus (Histamine)

  8. Locus ceruleus (Noradrenaline)

  9. Dorsal raphe (Serotonin)

 


DURING REM (RAPID EYE MOVEMENT) SLEEP CYCLE:

 

  • MELATONIN —-> INHIBITS —->¬†Basal forebrain (Acetylcholine) AND¬†Suprachiasmatic nucleus.

  • ADENOSINE —->¬†INHIBITS —->¬†Basal forebrain (Acetylcholine).

  • ADENOSINE —->¬†STIMULATES —-> VLPO

  • VLPO —-> INHIBITS —->¬†TMN (Histamine) AND¬†Locus ceruleus (Noradrenaline) AND¬†Dorsal raphe (Serotonin).

 


SLEEP EEG CHANGES IN MAJOR DEPRESSION:

 

(1) Impaired sleep continuity:

  • Increase of sleep latency

  • Elevated number of intermittent awakenings

  • Early morning awakening.

 

(2) Disinhibited REM sleep:

  • Shortened REM latency, or sleep onset REM period (SOREMP; REM latency 0‚Äď20 minutes)

  • Prolonged first REM period, and

  • Elevated REM density particularly during the first REM period.

 

 


UNDERLYING MECHANISM:

 

  1. Brainstem norepinephrine and serotonin systems suppress both REM sleep and depressive phenomenon.

  2. Acetylcholine systems promote both REM and depressive phenomenon and

  3. In control of depressive phenomena, as acetylcholine neuronal systems interact and the balance of activity between these two systems, rather than absolute activity levels in either, is the critical factor.

 


ROLE OF ANTIDEPRESSANTS ON SLEEP:

 

  • Antidepressants with Improved Sleep Continuity: sedating antidepressants e.g., TCAs.

  • Antidepressants with Alerting Effect & Inducing Arousal in Sleep: SSRIs, venlafaxine, bupropion and phenelzine.

  • Antidepressants with¬†5-HT2C¬†antagonist properties: promote slow wave sleep.

  • Antidepressants Decreasing Slow Wave Sleep: clomipramine, imipramine.

  • SSRIs: (a) no effect on slow wave sleep, (b) increase intermittent wakefulness and (c) impairs sleep continuity.

  • Antidepressants Not Suppressing REM:¬†trimipramine, bupropion, mirtazapine and tianeptine.

  • Antidepressant resulting in total abolishment of REM sleep: clomipramine, phenelzine and tranylcypromine.¬†

  • Antidepressants resulting in nearly total REM suppression: vilazodone.

 


SOURCE:
  1. Dialogues Clin Neurosci. 2005 Dec; 7(4): 323‚Äď334.
  2. Am J Psychiatry. 1982 May;139(5):565-70.
  3. CNS Drugs January 1999, Volume 11, Issue 1, pp 49‚Äď60.
  4. ChronoPhysiology and Therapy. 29 April 2015 Volume 2015:5 Pages 15‚ÄĒ25.

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Dr. Harvinder Singh, M.D. (Admin)


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