Low dose of aripiprazole advanced sleep rhythm and reduced nocturnal sleep time in the patients with delayed sleep phase syndrome: an open-labeled clinical observation

Figures & data

Table 1 Demographic data and sleep parameters of the patients with DSPS and depressive symptoms

No	Age (years)/gender	Primary diagnosis	Comorbidity	Sleep onset (hours)		Midpoint of sleep (hours)		Sleep offset (hours)		Total sleep time (hours)		APZ (mg)		Other medications
				Pre-treatment (Pre-T)	Post-treatment (Post-T)	Pre-T	Post-T	Pre-T	Post-T	Pre-T	Post-T	Initial dose	Final dose
1	43/M	Irregular sleep wake pattern − → DSPS	MDD	26 (2 am)	25 (1 am)	6.25	4.25	10.5	7.5	8.5	6.5	3	1.5	Valproate 600 mg, mianserin 30 mg, paroxetine 20 mg, brotizolam 0.25 mg, ramelteon 8 mg, methylcobalamin 250 µg
2	27/M	DSPS	MDD	25 (1 am)	23	6.5	2.5	12	6	11	7	1.5	1.5	Mirtazapine 7.5 mg, escitalopram 20 mg, rilmazafone 1 mg, methylcobalamin 150 µg, quetiapine 150 mg, ramelteon 4 mg
3	48/F	DSPS	MDD	25 (1 am)	24 (0 am)	4.5	3	8	6	7	6	1.5	0.75	Paroxetine CR 50 mg, clotiazepam 15 mg, alprazolam 2.4 mg, zolpidem 5 mg, brotizolam 0.25 mg, suvorexant 20 mg, methylcobalamin 1,500 µg
4	50/F	DSPS	MDD	29 (5 am)	27 (3 am)	8.5	6.5	12	10	7	7	3	1.5	Sertraline 50 mg, alprazolam 0.8 mg, etizolam 1.5 mg, triazolam 0.25 mg
5	55/M	DSPS	MDD	22.5	24 (0 am)	2	2.75	5.5	5.5	7	5.5	0.75	0.5	Milnacipran 150 mg, paroxetine 40 mg, sulpiride 150 mg, valproate 200 mg, brotizolam 0.25 mg ramelteon 4 mg
6	64/F	DSPS	MDD	25 (1 am)	23	5.5	3.5	10	8	9	9	1	1	Sertraline 100 mg, etizolam 1 mg, flunitrazepam 2 mg, levomepromazine 25 mg, ramelteon 8 mg
7	28/M	DSPS	MDD	24 (0 am)	23.5	4.25	3	8.5	6.5	8.5	7	0.5	0.5	Duloxetine 60 mg, mirtazapine 15 mg, blomazepam 1 mg, zolpidem 5 mg
8	44/F	DSPS	Dysthymia	26 (2 am)	24 (0 am)	5.5	3	9	6	6.5	6	3	3	Milnacipran 50 mg, mirtazapine 7.5 mg, triazolam 0.25 mg, etizolam 0.5 mg, diazepam 4 mg, methylcobalamin 150 µg, ramelteon 4 mg
9	34/M	DSPS	Dysthymia	23	Drop out			8		9		1.5		Olanzapine 5 mg, rolazepam 2 mg, methylcobalamin 150 µg
10	27/M	DSPS	Dysthymia	25 (1 am)	Drop out			9		8		3		Ramelteon 4 mg, methylcobalamin 150 µg
11	19/M	DSPS	(−)	25 (1 am)	25 (1 am)	6	4.5	11	8	10	7	1.5	1	None
12	23/M	DSPS	(–)	29 (5 am)	27 (3 am)	8.5	6.75	12	10.5	7	7.5	1	0.5	None
DSPS mean	38.5			25.7 (1.7 am)	24.6 (0.6 am)	5.8	4.0	9.6	7.4	8.2	6.9	1.8	1.2
SD	14.2			2.0	1.5	1.9	1.5	2.0	1.7	1.4	1.0	1.0	0.8
Treatment difference				1.1		1.8		2.5		1.3
SD				1.2		1.3		1.7		1.4
p-value				p=0.021		p=0.001		p=0.0007		p=0.018

Abbreviations: DSPS, delayed sleep phase syndrome; APZ, aripiprazole; MDD, major depressive order.

Figure 1 The sleep diary of case 1. (A) Upper part is 3 weeks period of initial visit about 4 years before. (B) Middle part is 2 weeks period of pretreatment with APZ. (C) Lower part is 2 weeks period during treatment. The left and right ends are 0 am. Sleep time during 24 hours is indicated by black bars and drowsy period is indicated by shadow bars. (A) In the period of pretreatment, the sleep diary showed irregular sleep–wake pattern in the 3–4 years before. We started ramelteon (melatonin analog), methylcobalamin, paroxetine, etc. (B) His sleep pattern became DSPS with 8.5 hours sleep time with abovementioned medications. (C) After treatment with 3 mg of APZ at evening, he started to sleep around 1 am and got up around 7:30 am.

Abbreviations: DSPS, delayed sleep phase syndrome; APZ, aripiprazole.