The role of paliperidone extended release for the treatment of bipolar disorder

Figures & data

Table 1 Medications FDA approved for bipolar disorder

Pharmacologic class and medication	FDA-approved indications
	Acute mania	Acute depression	Mixed symptoms	Maintenance treatment
Group 1A alkaline metals
Lithium	✓a			✓a
First-generation antipsychotics
Chlorpromazine	✓b
Second-generation antipsychotics
Olanzapine	✓c		✓	✓
Olanzapine/Fluoxetine combination		✓a
Risperidone	✓c		✓c
Risperidone long-acting intramuscular injection				✓a
Quetiapine (immediate release and extended release)	✓c	✓a	✓c	✓d
Ziprasidone	✓a		✓a	✓d
Aripiprazole	✓c		✓c	✓c
Asenapine	✓c		✓c
Antiepileptic medications
Lamotrigine				✓a
Divalproex (immediate release and extended release)	✓a		✓a
Carbamazepine extended release	✓a		✓a

Notes:

a FDA approved as a monotherapy;

b FDA approved to control the manifestations of the manic type of manic-depressive illness;

c FDA approved as a monotherapy or as an adjunct treatment to lithium or valproate;

d FDA approved only as an adjunct to lithium or divalproex sodium for maintenance.

Abbreviation: FDA, US Food and Drug Administration.

Table 2 Summary of clinical studies with paliperidone extended release in acute mania^32–34

Study	N	Change in mean (SD) YMRS total score	Difference in LS mean changea
			95% CI	P value
Monotherapy
Berwaerts et al^Citation32	443
Paliperidone ER 3 mg	107	−9.1 (11.18)	−1.0 (−1.59, 3.58)	0.79
Paliperidone ER 6 mg	112	−11.4 (9.98)	−1.4 (−3.98, 1.15)	0.57
Paliperidone ER 12 mg	109	−13.8 (9.67)b	−3.6 (−6.99, 0.30)	0.025
Placebo	115	−9.8 (10.60)
Vieta et al^Citation33	486
Paliperidone ER 3–12 mg	190	−13.2 (8.68)	−5.5 (−7.57, 3.35)	0.001
Quetiapine 400–800 mg	192	−11.7 (9.28)	−4.2 (6.45, −1.95)	0.001
Placebo	104	−7.4 (10.74)
Adjunct
Berwaerts et al^Citation34	299
Paliperidone ER plus MS	149	−14.3 (10.01)	−1.36 (−3.27, 0.54)	0.16
MS monotherapy plus placebo	150	−13.2 (10.91)

Notes:

a All least square means change versus placebo, except Berwaerts et al adjunctive study: combo vs monotherapy;

b P value = 0.005.

Abbreviations: CI, confidence interval; ER, extended release; LS, least squares; MS, mood stabilizer (lithium or valproate); SD, standard deviation; YMRS, Young Mania Rating Scale.

Table 3 Treatment-emergent adverse events (TEAEs) during double-blind controlled trials of paliperidone extended release (ER) for bipolar disorder^32–34

	Overall TEAEs	Possibly related TEAEs	TEAEs leading to death	1 or more serious TEAEs	TEAEs leading to discontinuation
Monotherapy
Berwaerts et al^Citation32
Placebo (n = 121) n (%)	85 (70)	49 (40)	0	10 (8)	6 (5)
Paliperidone ER 3 mg (n = 112) n (%)	68 (61)	45 (40)	0	4 (4)	1 (1)
Paliperidone ER 6 mg (n = 119) n (%)	89 (75)	64 (54)	0	5 (4)	13 (11)
Paliperidone ER 12 mg (n = 115) n (%)	100 (87)	68 (59)	0	5 (4)	9 (8)
Total (n = 467) n (%)	342 (73)	226 (48)	0	24 (5)	29 (6)
Vieta et al^Citation33
Placebo/paliperidone ER (n = 105) n (%)	75 (71)	50 (48)	1 (1)	8 (8)	7 (7)
Paliperidone ER (n = 194) n (%)	136 (70)	113 (58)	0	16 (8)	18 (9)
Quetiapine (n = 192) n (%)	157 (82)	122 (64)	1 (1)	14 (7)	12 (6)
Total (n = 491) n (%)	368 (75)	285 (58)	2 (<1)	38 (8)	37 (8)
Adjunct
Berwaerts et al^Citation34
MS + Placebo (n = 150) n (%)	81 (54)	39 (26)	NR	7 (5)	2 (1)
MS + Paliperidone ER (n = 149) n (%)	104 (70)	62 (42)	NR	7 (5)	12 (8)

Abbreviation: MS, mood stabilizer (lithium or valproate).

BerwaertsJXuHNuamahILimPHoughDEvaluation of the efficacy and safety of paliperidone extended-release in the treatment of acute mania: a randomized, double-blind, dose-response studyJ Affect Disord20121361–2e51e6020624657

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BerwaertsJLaneRNuamahIFPaliperidone extended-release as adjunctive therapy to lithium or valproate in the treatment of acute mania: a randomized, placebo-controlled studyJ Affect Disord20111291–325226020947174

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VietaENuamahIFLimPA randomized, placebo- and active-controlled study of paliperidone extended release for the treatment of acute manic and mixed episodes of bipolar I disorderBipolar Disord201012323024320565430

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