Preventing the Onset of Major Depressive Disorder: A Meta-analytic Review of Psychological Interventions

Kim van Zoonen; Claudia Buntrock; David Daniel Ebert; Filip Smit; Charles F Reynolds III; Aartjan TF Beekman; Pim Cuijpers

Disclosures

Int J Epidemiol. 2014;43(2):318-329.

Discussion

We examined whether preventive interventions are effective in reducing the incidence of MDD. Results showed that preventive interventions lowered the incidence of depression by 21%, compared with controls. This is in agreement with the results of the previous meta-analyses conducted by Cuijpers et al. in 2008. A reduction in incidence of 21% can be considered clinically relevant. In the current meta-analysis we only included studies that used diagnostic criteria at baseline and follow-up, to exclude cases of depression at baseline and assess diagnostic status at follow-up. Using these rigorous criteria and the relatively large number of trials, this meta-analysis offers more robust evidence on the impact of preventive interventions on the incidence of new depressions than any previous meta-analysis.

The current meta-analyses did not show IPT to be more effective than CBT. This is in contrast to the findings of our earlier meta-analyses. Examining the NNT, however, shows that IPT (NNT = 7) is more effective than CBT (NNT = 71). Furthermore, there is no overlap in the 95% confidence intervals, reinforcing our suggestion that IPT might have a greater prophylactic effect than CBT. This result is consistent with our results from the previous meta-analysis conducted in 2008. It should, however, be interpreted with caution, since the number of studies using IPT^[5] was considerably lower than the studies using CBT.^[20] If IPT is indeed more effective, this might be related to the fact that this type of intervention focuses more directly on the current problems and high-risk situations. This might be exactly what people in high-risk situations or with subthreshold symptoms need.

Also, results did not suggest that indicated prevention (IRR = 0.74) was more effective than selective prevention (IRR = 0.81). However, only two studies investigated universal prevention and those were therefore excluded from analysis.

This does not necessarily imply that universal intervention might not be effective in high-risk subgroups. Rose^[58] proposed that there are two strategies to prevention: a population strategy of prevention, which targets a whole population regardless of individual differences in risk status; and an individual strategy of prevention, which targets individuals at high risk for an adverse health outcome.^[59] Our meta-analysis is mainly focused on individual prevention. If we used less rigorous inclusion criteria (e.g. no diagnostic instrument to determine whether participants have a diagnosis) we might find results similar to another meta-analysis conducted in 2012.^[60] This analysis found a beneficial effect in the prevention of postpartum depression in a range of interventions, individually based as well as multiple contacts. This shows that population-based strategies for prevention are interesting from a public health point of view and have the potential of reducing the incidence of depression considerably. However, our study also makes clear that there are no studies yet that show that population-based strategies actually reduce the incidence of depressive disorders.

Although prevention of depression seems to be effective, the NNT appears high (20 in the overall analysis), which is comparable to the NNT in the earlier analyses by Cuijpers (NNT = 22). There are, however, no normative thresholds for lower or higher NNT.^[13] Considering the impact depressive disorders have on social, economic and physical life and the clinical relevance, it seems an acceptable number. As discussed earlier, universal prevention might have a very different approach and yield very different results compared with selective and indicated prevention. Also, there were only two studies using universal prevention in this analysis. Therefore, it might be a consideration to not include universal prevention in other reviews like the current review. Other research did not show that the implemented intervention reduced the depressive symptoms in adolescents at high risk. The intervention was implemented in everyday life situations. The sample consisted of non-referred adolescents from the community. This study was, however, not included in the current meta-analysis because the researchers did not use a diagnostic instrument to diagnose depressive disorders at follow-up.^[61] However, the study shows that it is important to investigate the risk factors for depression, which could be due to premorbid vulnerability or due to the experience of previous episodes of depression. Future research should take history of depression into account.

Furthermore, the control/comparison groups in the included studies consisted mostly of treatments like care-as-usual or waiting-list. These are passive rather than active forms of 'treatments'. There is, therefore, no control for face-to-face time and attention. These are, however, nonspecific aspects of structured interventions like IPT or CBT. If future research included more active comparators, it would greatly improve the strength with which conclusions can be drawn about the specific prophylactic value of learning-based psychotherapies.

Most follow-up periods were between 6 and 12 months;^[28] only 2 studies had follow-up periods beyond 2 years. Therefore, it is not clear whether preventive interventions actually prevented the incidence of depression or simply delayed the onset of depressive episodes. We performed analyses per follow-up (<5, 6, 7–12, ≥13 months). Comparing the effects of preventive interventions and first follow-up months showed a small positive association, indicating that the more months pass, the more effective the preventive intervention is. However, comparing the effects of preventive interventions and last follow-up period, this had a very small negative association. This might indicate that the effects of the preventive intervention became smaller over longer follow-up periods, uggesting that the preventive interventions delay the onset of disorders rather than preventing them altogether. However, only few studies had longer follow-up periods than 2 years. From a clinical point of view, preventing new onsets of depression would obviously be preferable since it would completely avoid the burden of disease in all prevented cases. However, delaying the onset is also important. Every year a disorder is delayed is a year without suffering.

We acknowledge several limitations of this study. First, several studies examined different populations and used different types of interventions. That said, according to the I ² statistic, heterogeneity was low to moderate, indicating that it may be a fairly homogeneous set of studies. Second, the follow-up periods differed between studies. We therefore examined the various follow-up periods. However, we also conducted regression analysis with only the first follow-up occasion and regression analysis with only the last follow-up occasion to see whether there was any effect of decay over time. Third, the numbers of studies in some of the subgroup-analyses were rather small and show only correlations. Therefore results should be interpreted with caution.

In conclusion, it is encouraging that we found positive effects of preventive interventions on the incidence of major depression, which are clinically relevant. Prevention of depressive disorders is possible, and may, in addition to treatment, be an important way to further reduce the burden of disease due to a very prevalent and disabling condition: depression.

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Table 1. Selected characteristics of studies examining the effects of interventions on the incidence of new cases of depressive disorders
Study	Type	Recruitment	Target population	Inclusion criteria	Prevented disorder	Conditions	n	Intervention	FU (mn)	Drop-out (%)	ITT
Allart et al. 2007³⁴	Ind	Community	Adults	BDI ≥10; no current MDD	MDD	1. CBT	61	12 CBT group sessions	12	25	Yes
Allart et al. 2007³⁴	Ind	Community	Adults	BDI ≥10; no current MDD	MDD	2. CAU	41	12 CBT group sessions	12	25	Yes
Arnarson & Craighead 2009¹⁵	Ind	Screening at schools	Adolescents	CDI, CASQ ≥; no current DD	MDD	1. Eclectic	81	14 eclectic group sessions	12	34	No
Arnarson & Craighead 2009¹⁵	Ind	Screening at schools	Adolescents	CDI, CASQ ≥; no current DD	MDD	2. CAU	90	14 eclectic group sessions	12	34	No
Austin et al. 2008²⁴	Sel	Antenatal clinics	Antenatal women	EPDS > 10; ANRQ > 23; hx of DD	Anxiety and PMDD	1. CBT	191	6 CBT group sessions + 1 booster	4	52	Yes
Austin et al. 2008²⁴	Sel	Antenatal clinics	Antenatal women	EPDS > 10; ANRQ > 23; hx of DD	Anxiety and PMDD	2. Booklet	86	6 CBT group sessions + 1 booster	4	52	Yes
Bot et al. 2010³⁵	Ind	outpatient clinics	People with diabetes	≥ 55 years; ≥ 16 CES-D	MDD	1. Stepped care	58	12 weeks	24	36	No
Bot et al. 2010³⁵	Ind	outpatient clinics	People with diabetes	≥ 55 years; ≥ 16 CES-D	MDD	2. CAU	56	12 weeks	24	36	No
Brugha et al. 2000³⁶	Sel	Screening	Primiparous women	Risk factor for depression	MDE	1. CBT	94	6 CBT + PST support group sessions	3	9	Yes
Brugha et al. 2000³⁶	Sel	Screening	Primiparous women	Risk factor for depression	MDE	2. CAU	96	6 CBT + PST support group sessions	3	9	Yes
Clarke et al. 1995³⁷	Ind	schools	Adolescents (15_16 years)	CES-D > 24;no current MDD/DYS	MDD + Dysthymia	1. CBT	55	15 CBT group sessions	12	27	No
Clarke et al. 1995³⁷	Ind	schools	Adolescents (15_16 years)	CES-D > 24;no current MDD/DYS	MDD + Dysthymia	2. CAU	70	15 CBT group sessions	12	27	No
Clarke et al. 2001¹⁴	Ind	HMO	Adolescents (13–18 years)	CES-D > 24; ≥1 DSM-IV	MDD + Dysthymia	1. CBT	43	15 CBT group sessions	24	17	Yes
Clarke et al. 2001¹⁴	Ind	HMO	Adolescents (13–18 years)	CES-D > 24; ≥1 DSM-IV	MDD + Dysthymia	2. CAU	47	15 CBT group sessions	24	17	Yes
Compas et al. 2009³⁸	Sel	Mental health clinics	Adolescents (9_15 years)	CESD/K-SADS-PL	MDE	1. CBT	56	12 sessions, four families each group	24	22	Yes
Compas et al. 2009³⁸	Sel	Mental health clinics	Adolescents (9_15 years)	CESD/K-SADS-PL	MDE	2. Written info	53	12 sessions, four families each group	24	22	Yes
De Jonge et al. 2009⁴⁰	Ind	Hospital	Patients with physical illness	CES-D, MINI	MDD	1. Nurse-led	47	Counsel or psychotherapy or case conference	12	33	Yes
De Jonge et al. 2009⁴⁰	Ind	Hospital	Patients with physical illness	CES-D, MINI	MDD	2. CAU	53	Counsel or psychotherapy or case conference	12	33	Yes
Elliott et al. 2000¹⁶	Sel	Screening	Pregnant women	Vulnerable (LQ)	PMDD	1. PE	47	11 PE sessions + mutual support	3	15	No
Elliott et al. 2000¹⁶	Sel	Screening	Pregnant women	Vulnerable (LQ)	PMDD	2. CAU	53	11 PE sessions + mutual support	3	15	No
Garber et al. 2009¹⁷	Ind	Universities and health centres	Adolescent (13–17) of parents with depression	CESD > 20 and/or 2 mn remission from MDD or both	MDD	1. CBT	159	8 CBT group sessions + 6 continuation sessions	9	9	Yes
Garber et al. 2009¹⁷	Ind	Universities and health centres	Adolescent (13–17) of parents with depression	CESD > 20 and/or 2 mn remission from MDD or both	MDD	2. CAU	157	8 CBT group sessions + 6 continuation sessions	9	9	Yes
Garcia et al. 2010⁴¹	Sel	Primary care	Primary care patients	18-65 yrs; SPPI no DSM-IV Axis	Somatoform disorders	1. Psycho- educational	52	Five 120-min group sessions by family doctor	60	21	No
Garcia et al. 2010⁴¹	Sel	Primary care	Primary care patients	18-65 yrs; SPPI no DSM-IV Axis	Somatoform disorders	2. No intervent.	52	Five 120-min group sessions by family doctor	60	21	No
Gillham et al. 2006¹⁸	Ind	Through HMO	Early adolescents (11–12 years)	CDI ≥ 7/9; no current MDD DYS	MDD, DYS	1. CBT	147	12 CBT group sessions	24	41	Yes
Gillham et al. 2006¹⁸	Ind	Through HMO	Early adolescents (11–12 years)	CDI ≥ 7/9; no current MDD DYS	MDD, DYS	2. CAU	124	12 CBT group sessions	24	41	Yes
Hagan et al. 2004²³	Sel	Neonatal unit	Mothers very preterm babies	No current DD	Postpartum depression	1. CBT	101	6 CBT group sessions + PE	12	12	Yes
Hagan et al. 2004²³	Sel	Neonatal unit	Mothers very preterm babies	No current DD	Postpartum depression	2. CAU	98	6 CBT group sessions + PE	12	12	Yes
Joling et al. 2012⁴²	Sel	Memory clinics, general practices, home care settings	Caregivers dementia patients	MINI	depressive or anxiety disorder	1. Family meetings	96	6 in-person counselling meetings once every 2 to 3 months	12	26	Yes
Joling et al. 2012⁴²	Sel	Memory clinics, general practices, home care settings	Caregivers dementia patients	MINI	depressive or anxiety disorder	2. CAU	96	6 in-person counselling meetings once every 2 to 3 months	12	26	Yes
Konnert et al. 2009⁴³	Ind	Residents of nursing homes	Nursing home residents (over 60 years)	No MDE, GDS ≥ 9	MDD	1. CBT	20	13 CBT sessions	6	33	No
Konnert et al. 2009⁴³	Ind	Residents of nursing homes	Nursing home residents (over 60 years)	No MDE, GDS ≥ 9	MDD	2. CAU	23	13 CBT sessions	6	33	No
Lara et al. 2009⁴⁴	Ind	Hospital, clinic and community health care centre	Pregnant women in Mexico	CES-D ≥ 16 and/or self-report hx of MDD	MDD	1. CBT	250	8 PE group sessions	4-9	64	Yes
Lara et al. 2009⁴⁴	Ind	Hospital, clinic and community health care centre	Pregnant women in Mexico	CES-D ≥ 16 and/or self-report hx of MDD	MDD	2. CAU	127	8 PE group sessions	4-9	64	Yes
Martinovic et al. 2006⁴⁵	Sel	Community + clinic	Adolescents (13–19) with epilepsy	sD; no current DD	MDD	1. CBT	15	12 CBT group sessions	9	6	Yes
Martinovic et al. 2006⁴⁵	Sel	Community + clinic	Adolescents (13–19) with epilepsy	sD; no current DD	MDD	2. CAU	15	12 CBT group sessions	9	6	Yes
Muñoz et al. 1995⁴⁶	Sel	General practice records	GP patients	No MDD in past 6 mn	MDD, dysthymia	1. CBT	72	8 CBT group sessions (CWD)	12	8	No
Muñoz et al. 1995⁴⁶	Sel	General practice records	GP patients	No MDD in past 6 mn	MDD, dysthymia	2. CAU	78	8 CBT group sessions (CWD)	12	8	No
Muñoz et al. 2007⁴⁷	Ind	Screening	Pregnant Latina women	CES-D ≥ 16; past history of MDD	PMDD	1. CBT	21	12 CBT group sessions (CWD)	12	9	No
Muñoz et al. 2007⁴⁷	Ind	Screening	Pregnant Latina women	CES-D ≥ 16; past history of MDD	PMDD	2. CAU	20	12 CBT group sessions (CWD)	12	9	No
Robinson et al. 2008⁴⁸	Sel	Community, universities & hospitals	Post-stroke patients	No current DD, HAM-D < 11; SCID	Poststroke depression	1. PST	59	6 PST session + 6 booster sessions	12	9	Yes
Robinson et al. 2008⁴⁸	Sel	Community, universities & hospitals	Post-stroke patients	No current DD, HAM-D < 11; SCID	Poststroke depression	2. Placebo	58	6 PST session + 6 booster sessions	12	9	Yes
Rovner et al. 2007⁴⁹	Sel	Screening in outpatient centres	Older patients	No current DD; SADS	MDD or minor depression	1. PST	95	6 individual PST sessions	6	13	Nes
Rovner et al. 2007⁴⁹	Sel	Screening in outpatient centres	Older patients	No current DD; SADS	MDD or minor depression	2. CAU	99	6 individual PST sessions	6	13	Nes
Seligman et al. 1999⁵⁰	Sel	All new students	Undergraduate students	ASQ = bottom quartile, no current MDD	MDD	1. CBT	106	8 CBT group sessions	36	4	No
Seligman et al. 1999⁵⁰	Sel	All new students	Undergraduate students	ASQ = bottom quartile, no current MDD	MDD	2. CAU	119	8 CBT group sessions	36	4	No
Sheffield et al. 2006²⁷	Uni/Ind	School	All students of 36 schools	High-symptom students, no MDD/DYS	MDD, dysthymia	1. CBT-Uni	107	8 CBT + 1 PST group lessons	18	15	No
						2. CBT-Ind	100
						3.CBT-Ind	110
						4. CAU	125
Spence et al. 2003²¹	Uni	School	Students of 18 high schools	ADIS-C	Major depression	1. CBT	751	8 grp lessons of CBT + ouPST	12	15	No
Spence et al. 2003²¹	Uni	School	Students of 18 high schools	ADIS-C	Major depression	2. CAU	749	8 grp lessons of CBT + ouPST	12	15	No
Van 't Veer-Tazelaar et al. 2009⁵¹	Ind	PIKO project	Older adults in primary care	No MDE;CES-D ≥16	MDD/anxiety	1. CBT + PST	86	3 months CBT + nurse calls/visits, then 7 PST sessions	24	24	Yes
Van 't Veer-Tazelaar et al. 2009⁵¹	Ind	PIKO project	Older adults in primary care	No MDE;CES-D ≥16	MDD/anxiety	2. CAU	84	3 months CBT + nurse calls/visits, then 7 PST sessions	24	24	Yes
Willemse et al. 2004⁵³	Ind	General practice	Adults (18–65 years)	One MDD core symptom, no MDD in past 6 mn (CIDI)	MDD, dysthymia	1. CBT	107	1 face-to-face contact + self-help book + 6 short phone consultations (CWD)	12	37	Yes
Willemse et al. 2004⁵³	Ind	General practice	Adults (18–65 years)	One MDD core symptom, no MDD in past 6 mn (CIDI)	MDD, dysthymia	2. CAU	109		12	37	Yes
Young et al. 2006¹⁹	Ind	School	Adolescents (15–16 years)	CES-D ≥ 16; 2 symptoms; no MDD/DYS	MDD, dysthymia (K-SADS)	1. IPT	27	2 individual + 8 IPT group sessions	6	2	Yes
Young et al. 2006¹⁹	Ind	School	Adolescents (15–16 years)	CES-D ≥ 16; 2 symptoms; no MDD/DYS	MDD, dysthymia (K-SADS)	2. CAU	14	2 individual + 8 IPT group sessions	6	2	Yes
Young et al. 2010⁵⁵	Ind	Two-stage screening	Adolescents (13–17 years)	CES-D 16 – 39; K-SADS-PI	MDD	1. IPT-AST	36	1. 2 pre-group sessions + 8 90-min group sessions	18	23	Yes
Young et al. 2010⁵⁵	Ind	Two-stage screening	Adolescents (13–17 years)	CES-D 16 – 39; K-SADS-PI	MDD	2. SC	21	2. 30-45 min individual counselling	18	23	Yes
Zlotnick et al. 2001⁵⁶	Sel	Hospitals	Pregnant women	≥1 risk indicators PDD, no MDD	PMDD	1. IPT	17	4 IPT group sessions	3	5	Yes
Zlotnick et al. 2001⁵⁶	Sel	Hospitals	Pregnant women	≥1 risk indicators PDD, no MDD	PMDD	2. CAU	18	4 IPT group sessions	3	5	Yes
Zlotnick et al. 2006²⁰	Sel	Hospitals	Pregnant women	High score risk survey, no current MDD	PMDD (LIFE)	1. IPT	17	4 IPT group sessions	3	13	No
Zlotnick et al. 2006²⁰	Sel	Hospitals	Pregnant women	High score risk survey, no current MDD	PMDD (LIFE)	2. CAU	46	4 IPT group sessions	3	13	No
Zlotnick et al. 2011⁵⁷	Sel	Primary care clinics + private OBGYN clinic	Pregnant women (18–40 years)	EPDS/SCID	MDD/PMDD	1. IPT	28	4 IPT + booster session	3	15	Yes
Zlotnick et al. 2011⁵⁷	Sel	Primary care clinics + private OBGYN clinic	Pregnant women (18–40 years)	EPDS/SCID	MDD/PMDD	2. CAU	26	4 IPT + booster session	3	15	Yes

ADIS-C, Anxiety disorders interview schedule children; ANRQ, Antenatal Risk Questionnaire; BDI, Beck Depression Inventory, (C) ASQ, (Children's) Attributional Style Questionnaire; CAU, care as usual; CBT, cognitive behavioural therapy; CDI, Children's Depression Inventory; CES-D = Centre for Epidemiological Studies-Depression Scale; CWD, Coping with depression; DAS, Dysfunctional Attitude Scale; DD, depressive disorder, DYS, dysthymia; EPDS, Edinburgh Postnatal Depression Scale; GDS, Geriatric Depression Scale; HAM-D, Hamilton rating scale Depression; HMO = Health Maintenance Program; IND, Indicated; IPT, Interpersonal therapy; K/SADS/PL, Kiddie-Sads-Present and Lifetime Version; LQ, Leverton Questionnaire; MDD, major depressive disorder; MDE, major depressive episode; MINI = Mini-International Neuropsychiatric Interview; mn, months; OBGYN, Obstetrics and gynaecology; PIKO = Prevention Intervention for Frail Elderly; PMDD, postpartum depression; PST, problem solving therapy; SADS, Schedule for Affective Disorders and Schizophrenia; SCID, Structured Clinical Interview for DSM-IV; sD = subthreshold depression; SEL, selective; SPPI = Standardized Polyvalent Psychiatric Interview; VAS, Visual Analogue Scale; Uni, universal.

Table 2. Meta-Analyses of studies examining the effects of preventive interventions on the incidence of depressive disorders: Incidence rate ratios, heterogeneity and numbers needed to treat (NNT) at 2 months to 5 years
		N	IRR	95% CI	I ²	95% CI	P	NNT	95% CI	P
Depressive disorders		34	0.79	0.69–0.91	24	0–50		20	13–37
Sheffield excluded		31	0.77	0.66–0.90	29	0–54		16	11–30
At first follow up		34	0.79	0.69–0.92	29	0–54		21	14–45
At last follow up		34	0.78	0.68–0.89	29	0–53		17	12–30
Follow up Period	<5 months	11	0.81	0.55–1.18	29	0–65		15	8–77
	6 months	6	0.51	0.30–0.86	41	0–76		15	5–14
	7–12 months	12	0.82	0.66–1.01	37	0–68		25	14–100
	>13 months	5	0.89	0.66–1.21	0	0–79		24	9–34
Subgroup analyses
Type of therapy	CBT	19	0.86	0.76–0.98	0	0–49	0.106	71	33–500	0.003
	IPT	5	0.36	0.13–0.96	32	0–74		7	4–20
	Other	10	0.68	0.49–0.95	52	1–77		12	7–37
Age	Students	14	0.81	0.67–0.97	25	0–60	0.231	22	13–71	0.419
	Adults	16	0.84	0.66–1.01	30	0–62		22	11–333
	Elderly	4	0.55	0.36–0.85	0	0–85		11	7–32
Target group^a	School-based	14	0.81	0.68–0.97	25	0–22	0.586	21	12–71	0.759
	Perinatal depression	9	0.81	0.59–1.11	22	0–63		20	10–71
	General Medical	10	0.69	0.54–0.89	0	0–62		15	9–42
	Other	1
Prevention type^a	IND	17	0.74	0.61–0.90	14	0–51	0.507	13	9–26	0.284
	SEL	15	0.81	0.65–1.01	26	0–60		21	12–91
	UNI	2
Number of sessions^a	1–7	10	0.81	0.61–1.07	51	0–76	0.775	20	11–125	0.159
	8–11	11	0.85	0.68–1.07	0	0–60		42	18–143
	≥12	12	0.75	0.58–0.97	9	0–48		14	9–31
	nr	1
Publication country	USA	14	0.67	0.54–0.82	0	0–55	0.051	13	9–25	0.002
	Europe	11	0.77	0.57–1.04	47	0–73		16	9–91
	Other	9	0.94	0.79–1.10	0	0–65		143	36–71
Quality score	<3	12	0.79	0.59–1.06	53	10–76	0.894	14	7.87–71	0.234
Quality score	3 or 4	22	0.77	0.67–0.90	0	0–46		29	19–71

Abbreviations: CBT, cognitive behavioral therapy; IND, indicated prevention; IPT, Interpersonal therapy; IRR, incidence rate ratio; I ², heterogeneity; MDD, major depressive disorder; N, number of studies; NNT, numbers needed to treat; NR, not reported; PMDD, postpartum major depressive disorder; SEL, selective prevention; UNI, universal prevention.
^aWhen subgroup included less than 3 studies analysis was done without that subgroup.