A review of quetiapine in combination with antidepressant therapy in patients with depression

Figures & data

Table 1 Published studies of augmentation of an antidepressant with quetiapine in patients with unipolar depression

Study	Design	N	Antidepressant/mood stabilizer	Quetiapine	Primary efficacy measure and result	Depression remission and response rates
Vavrusova 2002	4-week open-label	13	citalopram 40 mg/day	200 mg/day	MADRS, HAM-D, HAM-A, CGI, and PANSS; Significant improvement in depression, guilt, suicidal ideation, anxiety, sleep, and retardation	Not reported
Doree et al 2007	8-week, open-label	20	antidepressant plus lithium (n = 10) antidepressant plus quetiapine (n = 10)	up to 800 mg/day	Decrease in HAM-D and MADRS from baseline to endpoint; Mean HAM-D improved from 25.8 down to 4.4 and mean MADRS improved from 35.7 to 6.7	80% response rate on HAM-D and MADRS for quetiapine; 80% remission rate on HAM-D and MADRS for quetiapine
Adson et al 2004	9-week open-label, Subjects had comorbid anxiety disorder	MDD (n = 6); GAD (n = 5)	fluoxetine (n = 3) paroxetine (n = 4) sertraline (n = 1) citalopram (n = 3)	mean dose 180 mg/day	HAM-D, HAM-A, SAI baseline to endpoint; HAM-D significantly decreased from a mean of 20.27 to 5.64 HAM-A significantly reduced from 24.45 to mean of 5.82	10/11 (91%) responders
Yargic et al 2004	8-week, prospective, single-blind	112	Paroxetine alone (n = 54) Paroxetine plus quetiapine (n = 58)	up to200 mg/day	Decrease in HAM-D from baseline to endpoint; Decrease in HAM-D scores was significantly greater in combined therapy group than with paroxetine alone (p < 0.008)	Not reported
Hussain et al 2005	3-year, randomized, double blind	72	paroxetine monotherapy venlafaxine monotherapy paroxetine plus quetiapine venlafaxine plus quetiapine	not reported	Decrease in HAM-D from baseline to endpoint; Significant improvement in depressive symptoms and the development of remission occurred more frequently in the paroxetine plus quetiapine group	Not reported
Pathak et al 2005	case series in adolescents	10	fluoxetine (n = 3) venlafaxine (n = 1) sertraline (n = 4) citalopm (n = 1) escitalopram (n = 1)	mean dose 275 ± 190.4 mg/day	CGI improvement from baseline	7/10 (70%) responders
Targum et al 2005	4-week, open label	22	sertraline (n = 4) fluoxetine (n = 3) citalopram (n = 7) paroxetine (n = 3) venlafaxine (n = 5)	mean dose 105.9 ± 65.6 mg/day	Decrease in HAM-A and HAM-D from baseline to endpoint; Mean HAM-A significantly improved from 25.6 to 9.2(p < 0.001) and mean HAM-D improved from 15 to 7.2 (p < 0.001) at endpoint	Not reported
Devarajan et al 2006	naturalistic case series	6	sertraline (n = 6)	200–300 mg/day	HAM-D-21 baseline to endpoint; Addition of quetiapine improved ratings at week 5–6	6/6 (100%) responders 5/6 (83%) remitters
Sagud et al 2006	20-week, open-label	18	reboxetine + paroxetine (n = 2) reboxetine + sertraline (n = 1) paroxetine + maprotiline (n = 4) paroxetine (n = 2) fluvoxamine (n = 2) sertraline (n = 1) moclobemide (n = 1) carbamazepine (n = 3) lamotrigine (n = 2)	mean dose 315 ± 109 mg/day	Decrease in HAM-D from baseline; By wk 2, HAM-D insomnia subscale significantly reduced; by wk 4, HAM-D total score and anxiety subscale score significantly improved; by wk 5, HAM-D depressed mood subscale significantly reduced	14/18 (78%) responders 11/18 (61%) remitted
Baune et al 2007	4-week, open-label	MDD (n = 21); BPD (n = 6)	venlafaxine (n = 26); escitalopram (n = 1)	300–800 mg/day	Decrease in HAM-D from baseline to endpoint; Mean HAM-D significantly improved from 20.2 to 9.4 (p < 0.001) at endpoint	Not reported

Abbreviations: CGI, Clinical Global Improvement; GAD, generalized anxiety disorder; HAM-A, Hamilton Rating Scale for Anxiety; HAM-D, Hamilton Rating Scale for Depression; MADRS, Montgomery Asberg Depression Rating Scale; MDD, major depressive disorder; BPD, bipolar depressive disorder; PANSS, Positive and Negative Syndrome Scale; SAI, State Anxiety Inventory.

Table 2 Unpublished randomized studies of augmentation of an antidepressant with quetiapine in patients with unipolar depression

Study	Design	N	Antidepressant/mood stabilizer	Quetiapine	Primary efficacy measure and result	Depression remission and response rates
Khullar et al 2006*	8-week, randomized, placebo-controlled, double blind	16	SSRI/SNRI plus quetiapine SSRI/SNRI plus placebo	Average dose 350 mg/day	Change in HAM-D, HAM-A and MADRS from baseline to endpoint; Significantly greater mean change in HAM-D scores (−11.9 vs −4.9; p < 0.05) and MADRS scores(−14.9 vs −5.3; p < 0.05), in quetiapine vs placebo group	Not reported
Mattingly et al 2006*	8-week, randomized, placebo-controlled, double blind	36	SSRI/SNRI plus quetiapine SSRI/SNRI plus placebo	Mean dose 268 ± 71.1 mg/day	Decrease in HAM-D and MADRS from baseline to endpoint; Significant improvement in HAM-D scores (−16.7 vs −9.8; p < 0.01) and MADRS scores(−17 vs −8.7; p < 0.05), in quetiapine vs placebo group	HAM-D response 67% vs 27% HAM-D remission 43% vs 15%
McIntyre et al 2006*	8-week, randomized, placebo-controlled, double blind	58	SSRI/SNRI plus quetiapine SSRI/SNRI plus placebo	Mean dose 202 ± 93 mg/day	Decrease in HAM-D and HAM-A from baseline to endpoint; Significant improvement in HAM-D scores (−11.2 vs −5.5; p < 0.01) and HAM-A scores(−12.5 vs −5.9; p < 0.01), in quetiapine vs placebo group	HAM-D response 48% vs 28% HAM-D remission 31% vs 17% HAM-A response 62% vs 28% HAM-A remission 41% vs 17%

Abbreviations: HAM-A, Hamilton Rating Scale for Anxiety; HAM-D, Hamilton Rating Scale for Depression; MADRS, Montgomery Asberg Rating Scale for Depression; SNRI, selective norepinephrine reuptake inhibitor; SSRI, selective serotonin reuptake inhibitor.

* Investigator-initiated study with funding support obtained from Astra Zeneca.

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