Table 45-1 Clinical trials of augmentation strategies in unipolar depression

Table 45-1 Clinical trials of augmentation strategies in unipolar depression
Antidepressant	Investigators	N	Design	Augmenting agent	Daily dosage of augmenting agent	Response rate	Significantly greater than seen with placebo?
				Lithium
TCA, MIAN	Heninger et al. 1983	15	RCT	Lithium	900-1,200 mg	5 of 8 (63%)	Yes
TCA	Cournoyer et al. 1984	12	RCT; c/o	Lithium	900 mg	?	Yes
TCA	Kantor et al. 1986	7	RCT	Lithium	900 mg	1 of 4 (25%)	No
TCA, MAOI	Zusky et al. 1988	16	RCT	Lithium	≥300 mg	3 of 8 (38%)	No
TCA, SSRI, etc.	Schopf et al. 1989	27	RCT	Lithium	≥800 mg	7 of 14 (50%)	Yes
TCA	Stein and Bernadt 1993	34	RCT	Lithium	250 vs. 750 mg	6 of 34 (18%) vs. 15 of 34 (44%)	Yes, at higher dose
TCA	Joffe et al. 1993c	50	RCT	Lithium	900 mg	9 of 17 (53%)	Yes
TCA	de Montigny et al. 1983	10	RCT	Lithium	900 mg	5 of 5 (100%)	Yes
SSRI	M. Fava et al. 1994b	41	RCT	Lithium	300-600 mg	4 of 14 (29%)	—
SSRI, TCA	Katona et al. 1995	62	RCT	Lithium	≥400 mg	15 of 29 (52%)	Yes
SSRI	Baumann et al. 1996	24	RCT	Lithium	800 mg	6 of 10 (60%)	Yes
TCA	Browne et al. 1990	17	RCT	Lithium	900-1,200 mg	3 of 7 (43%)	No
				Thyroid hormone (T₃)
TCA	Targum et al. 1984	21	Open	T3	25 μg	7 of 21 (33%)	—
Imipramine	Gitlin et al. 1987	16	RCT	T3	25 μg	—^a	No
Imipramine	Thase et al. 1989b	20	Open	T3	25 μg	4 of 20 (20%)	—
TCA	Joffe et al. 1993c	50	RCT	T3	37.5 μg	9 of 17 (53%)	Yes
				Dopaminergic agents
SSRI, TCA, MAOI, etc.	Bouckoms and Mangini 1993	20	Open	Pergolide	? mg	11 of 20 (55%)	—
				Stimulants
MAOI	Fawcett et al. 1991	32	Open	Pemoline	18.75-112.5 mg	25 of 32 (78%)	—
				D-amphetamine	5-40 mg
Fluoxetine	Metz and Shader 1991	21	Open	Pemoline	9.375-37.5 mg	16 of 21 (76%)	—
				Buspirone
Fluoxetine	Jacobsen 1991	8	Open	Buspirone	30 mg	7 of 8 (87%)	—
SSRI	Joffe and Schuller 1993	25	Open	Buspirone	20-50 mg	17 of 25 (68%)	—
SSRI	Fischer et al. 1998	10	Open	Buspirone	30 mg	2 of 10 (20%)	—
SSRI	Landen et al. 1998	119	RCT	Buspirone	20-60 mg	29 of 57 (51%)	No
SSRI	Bouwer and Stein 1997	14	Retro	Buspirone	30 mg	6 of 14 (43%)	—
SSRI	Dimitriou and Dimitriou 1998	22	Open	Buspirone	20-30 mg	13 of 22 (59%)	—
				Pindolol
SSRI	Moreno et al. 1997	10	RCT; c/o	Pindolol	7.5 mg	0 of 10 (0%)	No
SSRI/Clomipramine	Perez et al. 1999	80	RCT	Pindolol	7.5 mg	5 of 40 (12.5%)	No
SSRI	Blier and Bergeron 1995	17	Open	Pindolol	7.5 mg	12 of 17 (70.5%)	—
SSRI	Maes et al. 1999	14	RCT	Pindolol	7.5 mg	?	?
				Mirtazapine
TCA, SSRI, etc.	Price et al. 1998	20	Open	Mirtazapine	15-30 mg	11 of 20 (55%)	—
				Atypical antipsychotics
SSRI	Ostroff and Nelson 1999	8	Open	Risperidone	0.5-1 mg	8 of 8 (100%)	—
Fluoxetine	Tollefson et al. 1999	28	RCT	Olanzapine	5-20 mg	?	?
				Anticonvulsants
Desipramine	Cullen et al. 1991	16	Retro	Carbamazepine	300 mg	7 of 16 (44%)	—
Note. TCA = tricyclic antidepressant; MIAN = mianserin; RCT = randomized clinical trial; Retro = retrospective; c/o = crossover; MAOI = monoamine oxidase inhibitor; SSRI = selective serotonin reuptake inhibitor; "—" indicates not applicable; "?" indicates not reported.
^a Response not measured in terms of % response/nonresponse and, also, no drug effect was observed.

Table 45-1 Clinical trials of augmentation strategies in unipolar depression
Antidepressant	Investigators	N	Design	Augmenting agent	Daily dosage of augmenting agent	Response rate	Significantly greater than seen with placebo?
				Lithium
TCA, MIAN	Heninger et al. 1983	15	RCT	Lithium	900-1,200 mg	5 of 8 (63%)	Yes
TCA	Cournoyer et al. 1984	12	RCT; c/o	Lithium	900 mg	?	Yes
TCA	Kantor et al. 1986	7	RCT	Lithium	900 mg	1 of 4 (25%)	No
TCA, MAOI	Zusky et al. 1988	16	RCT	Lithium	≥300 mg	3 of 8 (38%)	No
TCA, SSRI, etc.	Schopf et al. 1989	27	RCT	Lithium	≥800 mg	7 of 14 (50%)	Yes
TCA	Stein and Bernadt 1993	34	RCT	Lithium	250 vs. 750 mg	6 of 34 (18%) vs. 15 of 34 (44%)	Yes, at higher dose
TCA	Joffe et al. 1993c	50	RCT	Lithium	900 mg	9 of 17 (53%)	Yes
TCA	de Montigny et al. 1983	10	RCT	Lithium	900 mg	5 of 5 (100%)	Yes
SSRI	M. Fava et al. 1994b	41	RCT	Lithium	300-600 mg	4 of 14 (29%)	—
SSRI, TCA	Katona et al. 1995	62	RCT	Lithium	≥400 mg	15 of 29 (52%)	Yes
SSRI	Baumann et al. 1996	24	RCT	Lithium	800 mg	6 of 10 (60%)	Yes
TCA	Browne et al. 1990	17	RCT	Lithium	900-1,200 mg	3 of 7 (43%)	No
				Thyroid hormone (T₃)
TCA	Targum et al. 1984	21	Open	T3	25 μg	7 of 21 (33%)	—
Imipramine	Gitlin et al. 1987	16	RCT	T3	25 μg	—^a	No
Imipramine	Thase et al. 1989b	20	Open	T3	25 μg	4 of 20 (20%)	—
TCA	Joffe et al. 1993c	50	RCT	T3	37.5 μg	9 of 17 (53%)	Yes
				Dopaminergic agents
SSRI, TCA, MAOI, etc.	Bouckoms and Mangini 1993	20	Open	Pergolide	? mg	11 of 20 (55%)	—
				Stimulants
MAOI	Fawcett et al. 1991	32	Open	Pemoline	18.75-112.5 mg	25 of 32 (78%)	—
				D-amphetamine	5-40 mg
Fluoxetine	Metz and Shader 1991	21	Open	Pemoline	9.375-37.5 mg	16 of 21 (76%)	—
				Buspirone
Fluoxetine	Jacobsen 1991	8	Open	Buspirone	30 mg	7 of 8 (87%)	—
SSRI	Joffe and Schuller 1993	25	Open	Buspirone	20-50 mg	17 of 25 (68%)	—
SSRI	Fischer et al. 1998	10	Open	Buspirone	30 mg	2 of 10 (20%)	—
SSRI	Landen et al. 1998	119	RCT	Buspirone	20-60 mg	29 of 57 (51%)	No
SSRI	Bouwer and Stein 1997	14	Retro	Buspirone	30 mg	6 of 14 (43%)	—
SSRI	Dimitriou and Dimitriou 1998	22	Open	Buspirone	20-30 mg	13 of 22 (59%)	—
				Pindolol
SSRI	Moreno et al. 1997	10	RCT; c/o	Pindolol	7.5 mg	0 of 10 (0%)	No
SSRI/Clomipramine	Perez et al. 1999	80	RCT	Pindolol	7.5 mg	5 of 40 (12.5%)	No
SSRI	Blier and Bergeron 1995	17	Open	Pindolol	7.5 mg	12 of 17 (70.5%)	—
SSRI	Maes et al. 1999	14	RCT	Pindolol	7.5 mg	?	?
				Mirtazapine
TCA, SSRI, etc.	Price et al. 1998	20	Open	Mirtazapine	15-30 mg	11 of 20 (55%)	—
				Atypical antipsychotics
SSRI	Ostroff and Nelson 1999	8	Open	Risperidone	0.5-1 mg	8 of 8 (100%)	—
Fluoxetine	Tollefson et al. 1999	28	RCT	Olanzapine	5-20 mg	?	?
				Anticonvulsants
Desipramine	Cullen et al. 1991	16	Retro	Carbamazepine	300 mg	7 of 16 (44%)	—
Note. TCA = tricyclic antidepressant; MIAN = mianserin; RCT = randomized clinical trial; Retro = retrospective; c/o = crossover; MAOI = monoamine oxidase inhibitor; SSRI = selective serotonin reuptake inhibitor; "—" indicates not applicable; "?" indicates not reported.
^a Response not measured in terms of % response/nonresponse and, also, no drug effect was observed.