Adherence to augmentation therapy for the treatment of major depressive disorder

Figures & data

Figure 1. Flow diagram for identification and selection of study participants.

Table 1. Select demographic, comorbidity, and MDD-related healthcare characteristics.

		Total			Adjunctive Pharmacotherapy			Adjunctive Psychotherapy
		N =n	218,192%		N =n	185,349%		N =n	32,843%	p-value
Gender
	Female	161,700	74.1%		137,936	74.4%		23,764	72.4%	<0.01
	Male	56,492	25.9%		47,413	25.6%		9,079	27.6%
Age
	18–30	28,322	13.0%		21,394	11.5%		6,928	21.1%	<0.01
	31–49	79,835	36.6%		66,637	36.0%		13,198	40.2%
	50–64	96,937	44.4%		85,162	45.9%		11,775	35.9%
	65+	13,033	6.0%		12,094	6.5%		939	2.9%
	Unknown/Other	65	0.0%		62	0.0%		3	0.0%
MDD (most severe, baseline)
	Not specified	141,524	64.9%		129,124	69.7%		12,400	37.8%	<0.01
	Mild	8,068	3.7%		5,885	3.2%		2,183	6.6%
	Moderate	44,029	20.2%		31,267	16.9%		12,762	38.9%
	Severe	21,481	9.8%		16,479	8.9%		5,002	15.2%
	In remission	3,090	1.4%		2,594	1.4%		496	1.5%
Index antidepressant**
	SSRI	106,634	48.9%		87,096	47.0%		19,538	59.5%	<0.01
	SNRI	42,919	19.7%		36,675	19.8%		6,244	19.0%
	Bupropion	29,746	13.6%		25,853	13.9%		3,893	11.9%
	Serotonin modulators	22,028	10.1%		20,388	11.0%		1,640	5.0%
	Tricyclics/tetracyclics	13,325	6.1%		12,193	6.6%		1,132	3.4%
	Alpha 2s	3,456	1.6%		3,077	1.7%		379	1.2%
	MAOI	84	0.0%		67	0.0%		17	0.1%
Insurance
	Commercial	156,026	71.5%		132,958	71.7%		23,068	70.2%	<0.01
	Medicaid	62,166	28.5%		52,391	28.3%		9,775	29.8%
Adjunctive Pharmacotherapy
	SSRI	-	-		44,889	24.2%		-	-
	Antidepressants, other	-	-		37,116	20.0%		-	-
	Serotonin modulators	-	-		35,217	19.0%		-	-
	SNRI	-	-		23,829	12.9%		-	-
	Atypical antipsychotics	-	-		19,162	10.3%		-	-
	Tricyclics/tetracyclics	-	-		17,908	9.7%		-	-
	Alpha 2 receptor agonist	-	-		6,480	3.5%		-	-
	MAOI	-	-		748	0.4%		-	-
Dual Adjunctive Therapy*
	Yes	9,585	4.4%		4,876	2.6%		4,709	14.3%	<0.01
	No	208,607	95.6%		180,473	97.4%		28,134	85.7%
Psychiatric comorbidity
	Generalized anxiety disorder	103,036	47.2%		83,719	45.2%		19,317	58.8%	<0.01
	Substance-related disorders	44,693	20.5%		38,306	20.7%		6,387	19.4%	<0.01
	Insomnia	34,647	15.9%		31,538	17.0%		3,109	9.5%	<0.01
	Alcohol-related disorders	14,289	6.5%		11,212	6.0%		3,077	9.4%	<0.01
	Post-traumatic stress disorder	13,660	6.3%		9,411	5.1%		4,249	12.9%	<0.01
	Dysthymic disorder	12,313	5.6%		9,494	5.1%		2,819	8.6%	<0.01
	Panic attacks/disorder	10,993	5.0%		8,489	4.6%		2,504	7.6%	<0.01
Medical comorbidities
	Hypertension	87,503	40.1%		77,351	41.7%		10,152	30.9%	<0.01
	Lower back pain	77,403	35.5%		68,023	36.7%		9,380	28.6%	<0.01
	Hyperlipidemia	75,795	34.7%		66,949	36.1%		8,846	26.9%	<0.01
	Obesity	59,272	27.2%		51,035	27.5%		8,237	25.1%	<0.01
	COPD	51,131	23.4%		45,010	24.3%		6,121	18.6%	<0.01
	Fatigue	48,857	22.4%		42,633	23.0%		6,224	19.0%	<0.01
	Osteoarthritis	42,481	19.5%		37,761	20.4%		4,720	14.4%	<0.01
	Diabetes	41,356	19.0%		36,462	19.7%		4,894	14.9%	<0.01
	Asthma	27,760	12.7%		23,865	12.9%		3,895	11.9%	<0.01
	Anemia	26,986	12.4%		23,633	12.8%		3,353	10.2%	<0.01

* defined as adding both a 2nd medication (either an antidepressant or antipsychotic) and psychotherapy following an

initial antidepressant medication regimen.

** MDD: major depressive disorder; COPD: chronic obstructive pulmonary

disease; SSRI: selective serotonin reuptake inhibitor; SNRI: serotonin and norepinephrine reuptake inhibitor;

MAOI: monoamine oxidase inhibitor.

Table 2. Demographic characteristics and comorbidities among eligible participants with MDD, by adjunctive therapy.

			Pharmacotherapy							Psychotherapy
			Adherent			Non-Adherent				Adherent			Non-Adherent
			N =n/(mean)	67,148%/(SD)		N =n/(mean)	118,201%/(SD)	p-value		N =n/(mean)	18,024%/(SD)		N =n/(mean)	14,819%/(SD)	p-value
Gender
	Female		49,682	74.0%		88,253	74.7%	<0.01		12,972	72.0%		10,792	72.8%	ns
	Male		17,466	26.0%		29,948	25.3%			5,052	28.0%		4,027	27.2%
Age (mean, years)			49.8	(13.0)		47.7	(13.4)	<0.01		43.2	(13.5)		44.1	(13.9)	<0.01
Index antidepressant**
	SSRI		29,651	44.2%		57,445	48.6%	<0.01		10,667	59.2%		8,871	59.9%	<0.01
	SNRI		12,699	18.9%		23,976	20.3%			3,351	18.6%		2,893	19.5%
Serotonin modulators			8,814	13.1%		11,574	9.8%			895	5.0%		745	5.0%
Alpha 2 receptor agonist			1,178	1.8%		1,899	1.6%			215	1.2%		164	1.1%
Tricyclic or tetracyclic			5,043	7.5%		7,150	6.0%			630	3.5%		502	3.4%
Antidepressant, other			9,739	14.5%		16,114	13.6%			2,256	12.5%		1,637	11.0%
	MAOI		24	0.0%		43	0.0%			10	0.1%		7	0.0%
Dual Adjunctive Therapy*															<0.01
	Yes		2,972	4.4%		1,904	1.6%	<0.01		3,403	18.9%		1,306	8.8%
	No		64,176	95.6%		116,297	98.4%			14,621	81.1%		13,513	91.2%
Psychiatry visit															<0.01
	Yes		13,184	19.6%		26,325	22.3%	<0.01		7,479	41.5%		5,584	37.7%
	No		53,964	80.4%		91,876	77.7%			10,545	58.5%		9,235	62.3%
Psychiatric
Generalized anxiety disorder			11,743	17.5%		22,425	19.0%	<0.01		6,400	35.5%		4,828	32.6%	<0.01
Panic attacks/disorder			2,739	4.1%		5,750	4.9%	<0.01		1,395	7.7%		1,109	7.5%	ns
Post-traumatic stress disorder			3,032	4.5%		6,379	5.4%	<0.01		2,628	14.6%		1,621	10.9%	<0.01
	Dysthymic disorder		3,205	4.8%		6,289	5.3%	<0.01		1,665	9.2%		1,154	7.8%	<0.01
	Insomnia		10,841	16.1%		20,697	17.5%	<0.01		1,622	9.0%		1,487	10.0%	<0.01
Alcohol-related disorders			3,389	5.0%		7,823	6.6%	<0.01		1,787	9.9%		1,290	8.7%	<0.01
Substance-related disorders			12,471	18.6%		25,835	21.9%	<0.01		3,505	19.4%		2,882	19.4%	ns
Medical
	Hypertension		29,396	43.8%		47,955	40.6%	<0.01		5,228	29.0%		4,924	33.2%	<0.01
	Lower back pain		24,063	35.8%		43,960	37.2%	<0.01		4,905	27.2%		4,475	30.2%	<0.01
	Hyperlipidemia		26,143	38.9%		40,806	34.5%	<0.01		4,565	25.3%		4,281	28.9%	<0.01
	Obesity		19,529	29.1%		31,506	26.7%	<0.01		4,339	24.1%		3,898	26.3%	<0.01
	COPD		16,509	24.6%		28,501	24.1%	<0.05		3,192	17.7%		2,929	19.8%	<0.01
	Fatigue		14,917	22.2%		27,716	23.4%	<0.01		3,295	18.3%		2,929	19.8%	<0.01
	Osteoarthritis		14,419	21.5%		23,342	19.7%	<0.01		2,472	13.7%		2,248	15.2%	<0.01
	Diabetes		14,483	21.6%		21,979	18.6%	<0.01		2,536	14.1%		2,358	15.9%	<0.01
	Asthma		8,658	12.9%		15,207	12.9%	ns		2,098	11.6%		1,797	12.1%	ns
	Anemia		8,561	12.7%		15,072	12.8%	ns		1,778	9.9%		1,575	10.6%	<0.05

* defined as adding both a 2nd medication (either an antidepressant or antipsychotic) and psychotherapy following an

initial antidepressant medication regimen.

** MDD: major depressive disorder; COPD: chronic obstructive pulmonary

disease; SSRI: selective serotonin reuptake inhibitor; SNRI: serotonin and norepinephrine reuptake inhibitor;

MAOI: monoamine oxidase inhibitor

Figure 2. Adherence to adjunctive pharmacotherapy comparing individuals who did and did not add psychotherapy.

Figure 3. Adherence to adjunctive pharmacotherapy by therapeutic class.

Figure 4. Time (in days) from psychotherapy augmentation event to final psychotherapy visit.

Table 3. Logistic regression results for factors associated with adherence to adjunctive therapy.

			Adjunctive Pharmacotherapy				Adjunctive Psychotherapy
Characteristics	Level		O.R.		95% CI		O.R.		95% CI
Age
	18–30		1.0				1.0
	31–49		1.15		(1.11, 1.19)		-
	50–64		1.29		(1.24, 1.33)		-
	65+		1.39		(1.32, 1.46)		0.76		(0.66, 0.88)
Sex
	Male		1.0				1.0
	Female		0.94		(0.92, 0.96)		0.95		(0.90, 0.99)
Insurance							-
	Medicaid		1.0
	Commercial		0.95		(0.93, 0.98)		-
Dual Adjunctive Therapy*
	No		1.0				1.0
	Yes		3.03		(2.84, 3.22)		2.35		(2.19, 2.52)
Adjunctive Therapy**
	SSRI		1.0				N/A
	SNRI		0.83		(0.81, 0.86)
Serotonin modulator			0.36		(0.35, 0.37)
Alpha-2 receptor agonist			0.34		(0.32, 0.36)
Tricyclics and tetracyclics			0.36		(0.35, 0.38)
Antidepressant, other			0.59		(0.57, 0.61)
Atypical antipsychotics			0.46		(0.44, 0.47)
Adherence to index ADT
	≤0.59 PDC		1.0				1.0
	0.6–0.79 PDC		2.01		(1.96, 2.07)		1.06		(1.00, 1.13)
	0.8+ PDC		3.10		(3.02, 3.19)		1.13		(1.07, 1.20)
Psychiatry visit	No		1.0				1.0
	Yes		0.95		(0.92, 0.97)		1.09		(1.04, 1.15)
Comorbidities***
Substance use disorder			0.89		(0.86, 0.91)		-
Alcohol use disorder			0.85		(0.82, 0.89)		1.13		(1.05, 1.23)
	Anxiety		0.95		(0.93, 0.97)		-
Post-traumatic stress disorder			0.94		(0.90, 0.99)		1.34		(1.25, 1.44)
	Panic attacks		0.93		(0.88, 0.98)		-
Dysthymic disorder			0.91		(0.87, 0.95)		1.24		(1.14, 1.34)
	Hypertension		1.03		(1.01, 1.06)		0.88		(0.83, 0.93)
	Low back pain		0.96		(0.94, 0.98)		0.88		(0.84, 0.93)
	Hyperlipidemia		1.08		(1.06, 1.11)		0.92		(0.87, 0.98)
	Obesity		1.10		(1.07, 1.12)		-
	COPD		1.04		(1.01, 1.07)		0.93		(0.87, 0.98)
Most Recent MDD Diagnosis Severity
	Unspecified		1.0				1.0
	Severe		1.07		(1.03, 1.11)		1.12		(1.04, 1.20)
	Moderate		1.09		(1.06, 1.12)		1.15		(1.09, 1.21)
	Mild		ns				1.2		(1.09, 1.31)
	In remission		ns				1.2		(1.00, 1.45)

* defined as adding both a 2nd medication (either an antidepressant or antipsychotic) and psychotherapy following an initial antidepressant medication regimen. ** MDD: major depressive disorder; COPD: chronic obstructive pulmonary disease; SSRI: selective serotonin reuptake inhibitor; SNRI: serotonin and norepinephrine reuptake inhibitor; MAOI: monoamine oxidase inhibitor; PDC: proportion of days covered*** Odds ratio for a comorbidity is in comparison with absence of each condition.