Is the combination of a mood stabilizer plus an antipsychotic more effective than mono-therapies in long-term treatment of bipolar disorder? A systematic review

Buoli, Massimiliano; Serati, Marta; Altamura, Alfredo Carlo

doi:10.1016/j.jad.2013.08.024

Cited by 49 publications

(45 citation statements)

References 58 publications

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“…18 Actually, only level D evidence supports olanzapine in combination maintenance treatment. 16 Only one double-blind placebo controlled trial demonstrated the efficacy of olanzapine + MS. 19 Third, ziprasidone, which was approved for adjunctive maintenance treatment and was mentioned as a first line in CANMAT, was used very little (2.1%). It seems that ziprasidone was not preferred in acute treatment, and clinicians did not want to introduce a new drug during the maintenance period.…”

Section: Discussionmentioning

confidence: 99%

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Current prescription pattern of maintenance treatments for bipolar patients in Korea: A focus on the transition from acute treatments

Song

Kwon

Bahk

et al. 2015

Psychiatry Clin Neurosci

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Aims:We examined prescription patterns in maintenance treatment for recovered bipolar patients and compared these with acute treatments.Methods: Using retrospective methods, the bipolar patients in clinical recovery (Clinical Global Impression Bipolar Version score ≤ 2 for 6 months) after acute episode were selected. We reviewed differences between prescription patterns at remission and after a maintenance period of at least 6 months.Results: A total of 340 bipolar disorder patients were selected. During the maintenance period, more than half of the patients (192, 56.5%) took a mood stabilizer (MS) + antipsychotic (AP) combination. Among the MS, valproate (149, 43.8%) was most prescribed, and lithium (98, 28.8%) was second, but as patients moved into maintenance treatment, lithium use decreased, and the use of lamotrigine (86, 25.3%) increased. Preferred AP were quetiapine (125, 36.8%), aripiprazole (67, 19.7%), risperidone (48, 14.1%), and olanzapine (39, 11.5%). The use of olanzapine in maintenance was greatly decreased compared with that during acute treatment (67, 19.7%). Most patients did not take an antidepressant (AD), but the proportion using one or more AD was increased during maintenance (17.9% to 30.3%), and bupropion (28, 8.2%) was the preferred AD. Doses were decreased in all drugs, but lamotrigine was maintained at a dose of 133.2 ± 68.5 mg/day.

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Section: Discussionmentioning

confidence: 99%

“…Mean doses were 533.4 ± 256.6 mg/day for quetiapine, 16.8 ± 6.2 mg/day for olanzapine, 21.4 ± 9.2 mg/day for aripiprazole, and 4.8 ± 4.5 mg/day for risperidone. Among AD, bupropion (16,4.7%) was most preferred (Table 2).…”

Section: Demographic Data and Prescriptions At The Time Of Remissionmentioning

confidence: 99%

Current prescription pattern of maintenance treatments for bipolar patients in Korea: A focus on the transition from acute treatments

Song

Kwon

Bahk

et al. 2015

Psychiatry Clin Neurosci

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“…1-3 Acceptance of this strategy which promises better efficacy 4 despite a higher potential of adverse events 5,6 is reflected in increasing prescription trends. 7 Many pharmacokinetic drug-drug interactions (DDIs) have been identified by therapeutic drug monitoring (TDM) as TDM databases enable evaluation of pharmacokinetic DDIs in a representative population to get an insight into the safety and tolerability of combined psychopharmacological treatment.…”

Section: Discussionmentioning

confidence: 99%

“…Carbamazepine decreased serum concentrations of 9-OH-RIS and the AM when compared with the control group. In case of VPA and LMT, findings were less significant; hints for a weak RIS metabolism inhibition by LMT of unclear clinical significance were found.Key Words: therapeutic drug monitoring, risperidone, carbamazepine, valproic acid, lamotrigine cytochrome P450, interaction, pharmacokinetics (J Clin Psychopharmacol 2016;36: 00-00) G uidelines worldwide recommend the coadministration of second-generation antipsychotics as augmentative therapy to mood stabilizers or vice versa in the treatment of bipolar disorders, especially for the treatment of manic episodes.1-3 Acceptance of this strategy which promises better efficacy 4 despite a higher potential of adverse events 5,6 is reflected in increasing prescription trends. 7 Many pharmacokinetic drug-drug interactions (DDIs) have been identified by therapeutic drug monitoring (TDM) as TDM databases enable evaluation of pharmacokinetic DDIs in a representative population to get an insight into the safety and tolerability of combined psychopharmacological treatment.…”

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confidence: 99%

Pharmacokinetic Drug-Drug Interactions of Mood Stabilizers and Risperidone in Patients Under Combined Treatment

Schoretsanitis¹,

Haen²,

Gründer³

et al. 2016

J Clin Psychopharmacol

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Background: The combination of anticonvulsant mood stabilizers with antipsychotic drugs may lead to clinically relevant drug-drug interactions. The objective of the study was to identify pharmacokinetic interactions of different mood stabilizers on the metabolism of risperidone (RIS) under natural conditions.Methods: A large therapeutic drug monitoring database containing plasma concentrations of RIS and its metabolite 9-hydroxy-RIS (9-OH-RIS) of 1,584 adult patients was analyzed. Four groups (n = 1,072) were compared: a control group without a potentially cytochrome interacting comedication (R 0 , n = 852), a group comedicated with valproate (VPA) (R VPA , n = 153), a group comedicated with lamotrigine (LMT) (R LMT , n = 46), and a group under concomitant medication with carbamazepine (CBZ) (R CBZ , n = 21). Dose-adjusted plasma concentrations (C/D ratio) for RIS, 9-OH-RIS and active moiety (AM) (RIS + 9-OH-RIS), as well as metabolic ratios (RIS/9-OH-RIS) were computed.Results: Groups did not differ with regard to the daily dosage (P = 0.46).Differences were detected for the distributions of the C/D ratios for RIS, 9-OH-RIS and AM (P = 0.003, P < 0.001 and P < 0.001, respectively). Differences remained significant after conducting a Bonferroni correction (P = 0.0125). Pairwise comparisons of the concomitant medication groups with the control group revealed significant differences; RIS C/D ratios were significantly higher in the VPA and the LMT group than in the control group (P = 0.013; P = 0.021). However, these differences did not remain significant after Bonferroni correction. In contrast, CBZ-treated patients showed lower dose-adjusted plasma concentrations of 9-OH-RIS (P < 0.001) as well as the AM (P < 0.001) than the control group; this difference survived the Bonferroni correction. Conclusions:The data give evidence for pharmacokinetic interactions between RIS and different anticonvulsant mood stabilizers. Carbamazepine decreased serum concentrations of 9-OH-RIS and the AM when compared with the control group. In case of VPA and LMT, findings were less significant; hints for a weak RIS metabolism inhibition by LMT of unclear clinical significance were found.Key Words: therapeutic drug monitoring, risperidone, carbamazepine, valproic acid, lamotrigine cytochrome P450, interaction, pharmacokinetics (J Clin Psychopharmacol 2016;36: 00-00) G uidelines worldwide recommend the coadministration of second-generation antipsychotics as augmentative therapy to mood stabilizers or vice versa in the treatment of bipolar disorders, especially for the treatment of manic episodes.1-3 Acceptance of this strategy which promises better efficacy 4 despite a higher potential of adverse events 5,6 is reflected in increasing prescription trends. 7 Many pharmacokinetic drug-drug interactions (DDIs) have been identified by therapeutic drug monitoring (TDM) as TDM databases enable evaluation of pharmacokinetic DDIs in a representative population to get an insight into the safety and tolerability of combined psychopharmacological ...

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“…[7][8][9][10] It is estimated that nearly half of all BD patients who undergo pharmacological therapy still experience a relapse, accentuating the paucity of effective treatments for this highly diverse, complex illness. 11,12 Several studies, and APA guidelines, advise against removing medications in the remission (maintenance phase) of BD, 1,13 suggesting that doing so would significantly increase the risk of relapse, suicide, and morbidity. Trials indicating that manic or depressive episodes occur upon the withdrawal of BD medications are often designed to remove medications in an abrupt manner, without allowing prolonged tapering from the medication.…”

Section: Sinopsismentioning

confidence: 99%

Medication-free Alternatives for Long-term Maintenance of Bipolar Disorder: A Case Series

Gurevich¹,

Robinson

2015

Glob Adv Health Med

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Psychopharmacological treatment has been the mainstay in long-term maintenance of bipolar disorder (BD) patients for the last 60 years. Conventionally accepted treatment options are primarily based on expert opinion rather than on well-executed, independently funded research. Investigation of maintaining patients without medications using treatment alternatives has been neglected. This clinical case series examines the outcomes of 7 BD patients who experienced a poor response or significant side effects with conventional treatment modalities. Patients were gradually and safely withdrawn from all medications. Treatment strategies were based on an individualized holistic approach using herbs, nutritional supplements, vitamins, amino acids, acupuncture, dietary recommendations, and behavioral modifications. Multiple treatment modalities were combined addressing the etiological causes for BD symptoms. Upon withdrawal from psychotropic medications, patients were free of medication-induced side effects and obtained psychiatric stability for at least 10 months. Further research is needed to investigate the long-term outcomes of BD treatment modalities based on well-defined successful outcome criteria, such as reduction in symptoms, improvement in quality of life, overall health outcomes, and cost effectiveness.

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Is the combination of a mood stabilizer plus an antipsychotic more effective than mono-therapies in long-term treatment of bipolar disorder? A systematic review

Cited by 49 publications

References 58 publications

Current prescription pattern of maintenance treatments for bipolar patients in Korea: A focus on the transition from acute treatments

Current prescription pattern of maintenance treatments for bipolar patients in Korea: A focus on the transition from acute treatments

Pharmacokinetic Drug-Drug Interactions of Mood Stabilizers and Risperidone in Patients Under Combined Treatment

Medication-free Alternatives for Long-term Maintenance of Bipolar Disorder: A Case Series

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