Quetiapine and Bipolar Depression

Practice Issue

According to the National Institute of Mental Health, bipolar disorder mostly occurs in adulthood; however, children can be affected, too (“Bipolar disorder,” 2016). The disorder was previously known as manic-depressive illness; it is characterized by shifts in mood and emotional condition: people with bipolar disorder experience elated energized states during some periods and experience depressive and anxious states during other periods. It is assessed that the lifetime prevalence of all the types of the disorder combined amounts to two to four percent of the general population (Suttajit, Srisurapanont, Maneeton, & Maneeton, 2014). The disorder is not fully understood from the perspectives of etiology and pathophysiology, and treatment strategies and approaches vary in a wide range; however, an important part of treatment in many cases is the administration of medication aimed at improving patients’ psychological condition during depressive episodes. It is important because suicidal thoughts, along with lowered activity levels, memory and concentration problems, and insomnia, are among typical signs of a depressive episode in people with bipolar disorder.

Medication-related aspects of treating bipolar disorder are rather complicated because it may take years for a patient to find the combination of medications that will address the symptoms effectively in the patient’s individual case (Geddes & Miklowitz, 2013). Types of medications normally used in treatment include antidepressants, atypical antipsychotics, and mood stabilizers (Correll, Detraux, De Lepeleire, & De Hert, 2015). Atypical antipsychotics have been extensively used to treat psychiatric conditions; particularly, quetiapine was initially introduced in the context of searching for effective medications for schizophrenia (Suttajit et al., 2014). However, various studies had stressed the need to estimate the effects of this medication—used either as monotherapy or in combination with other medications—on people with bipolar disorder. Later, it was confirmed that quetiapine can be effective, and it was recommended as part of treating bipolar depressive conditions; however, not all the populations have been examined in this context. Specifically, the effect of reducing bipolar symptoms among children and adolescents has not been sufficiently analyzed. Although it has been observed that the medication can be effective for this population, and there is a low rate of adverse consequences, some authors, including Masi et al. (2015), claimed that the current knowledge about the risks associated with the use of quetiapine among children and adolescents, such as weight gain, is rather poor.

PICOT Question and Components

The PICOT question is formulated as follows: In children and adolescents aged 6-18, does the atypical pharmacological treatment with the use of quetiapine reduce bipolar 1 symptoms compared to the results of standardized pharmacological treatment, such as lithium or combination therapy, within 12 months? The specific PICOT components are presented below.

Population (P): Children and adolescents aged 6-18.
Intervention (I): Atypical pharmacological treatment of quetiapine monotherapy.
Comparison (C): Standard pharmacological treatment, such as lithium or combination therapies.
Outcome (O): Reduce bipolar 1 symptoms.
Timeframe (T): Within 12 months.

It should be noted that the type of bipolar disorder considered in the outcome component—bipolar 1—is characterized by explicit manic episodes that last for more than seven days or by symptoms associated with manic conditions that require professional care (“Bipolar disorder,” 2016). In patients with bipolar 1, depressive symptoms occur, too, and normally last for more than fourteen days.

Description of the Search

In the process of searching for relevant academic literature, keywords were used. In the Cumulative Index to Nursing and Allied Health Literature (CINAHL) database, the following combination was inputted in the search bar: “quetiapine” AND “children” AND “bipolar.” The use of quotation marks allowed ensuring that those articles will be found in which the exact forms of the three words are used. The use of the capitalized conjunction AND allowed ensuring that the articles displayed among search results will contain all three keywords. Initially, 13 articles were found; however, there was also the requirement to use recent sources (published within the last five years), which is why a limiter was used to display only those articles that were published during the indicated period. When the limiter was clicked, only four articles remained in the search results.

A similar process was adopted for the search process on the PubMed database website: same keywords and the five years publication date. A difference was that, for the PubMed database, it was also necessary to apply the limiter that allowed only those articles the full text of which was available for free. The further process of selecting materials from both databases is structurally presented in a PRISMA diagram (see Appendix A). A particularly important stage was the selection of articles that can be used to address the issue of interest (see PICOT Question and Components). First of all, some articles could be ruled out after reading the title; however, it was necessary for some of the found articles to read abstracts or take a look at certain sections in the body to identify information that can be used in addressing the PICOT question. When the selection process was completed, the selected articles were analyzed, and the result of the analysis is presented in an evidence review table (see Appendix B).

References

Bipolar disorder. (2016). Web.

Correll, C. U., Detraux, J., De Lepeleire, J., & De Hert, M. (2015). Effects of antipsychotics, antidepressants and mood stabilizers on risk for physical diseases in people with schizophrenia, depression and bipolar disorder. World Psychiatry, 14(2), 119-136.

Findling, R. L., Pathak, S., Earley, W. R., Liu, S., & DelBello, M. P. (2014). Efficacy and safety of extended-release quetiapine fumarate in youth with bipolar depression: An 8 week, double-blind, placebo-controlled trial. Journal of Child and Adolescent Psychopharmacology, 24(6), 325-335.

Geddes, J. R., & Miklowitz, D. J. (2013). Treatment of bipolar disorder. The Lancet, 381(9878), 1672-1682.

Habibi, N., Dodangi, N., & Nazeri, A. (2017). Comparison of the effect of lithium plus quetiapine with lithium plus risperidone in children and adolescents with bipolar I disorder: A randomized clinical trial. Medical Journal of the Islamic Republic of Iran, 31(1), 90-95.

Maneeton, B., Putthisri, S., Maneeton, N., Woottiluk, P., Suttajit, S., Charnsil, C., & Srisurapanont, M. (2017). Quetiapine monotherapy versus placebo in the treatment of children and adolescents with bipolar depression: A systematic review and meta-analysis. Neuropsychiatric Disease and Treatment, 13(1), 1023-1032.

Masi, G., Milone, A., Veltri, S., Iuliano, R., Pfanner, C., & Pisano, S. (2015). Use of quetiapine in children and adolescents. Pediatric Drugs, 17(2), 125-140.

Masi, G., Pisano, S., Pfanner, C., Milone, A., & Manfredi, A. (2013). Quetiapine monotherapy in adolescents with bipolar disorder comorbid with conduct disorder. Journal of Child and Adolescent Psychopharmacology, 23(8), 568-571.

Suttajit, S., Srisurapanont, M., Maneeton, N., & Maneeton, B. (2014). Quetiapine for acute bipolar depression: A systematic review and meta-analysis. Drug Design, Development and Therapy, 8(1), 827-838.

Appendix A

Appendix A

Appendix B

Evidence Review Table

PICOT Question: In children and adolescents aged 6-18, does the atypical pharmacological treatment with the use of quetiapine reduce bipolar 1 symptoms compared to the results of standardized pharmacological treatment, such as lithium or combination therapy, within 12 months?
Author(s), Year Objective/
Intervention, or Exposure Compared
Design Sample (n) Intervention Outcomes Studied (How Measured) Results Level of Evidence Rating (1-7)
Maneeton, B., Putthisri, S., Maneeton, N., Woottiluk, P., Suttajit, S., Charnsil, C., & Srisurapanont, M. (2017) Determining the efficacy and acceptability of quetiapine in the treatment of children and adolescents with bipolar depression. Systematic review 251 randomized patients (from all randomized controlled trials of bipolar depression in children and adolescents) Quetiapine as monotherapy was compared with a placebo. The doses, forms, and frequency of therapy were not limited and varied among studies considered in the review. Mean-changed score of a standardized depressive rating scale (Children’s Depression Rating Scale–Revised, CDRS-R), response and remission rate, Clinical Global Impression–Bipolar Version Severity (CGI-BP-S), discontinuation rates. The pooled mean-changed score of the quetiapine-treated group was not greater than that of the placebo-treated group. 5
PICO: Among children and adolescents, can quetiapine monotherapy, as opposed to placebo, increase the mean-changed score of a standardized depressive rating scale?
Findling, R. L., Pathak, S., Earley, W. R., Liu, S., & DelBello, M. (2013) To describe the safety, tolerability, and efficacy of quetiapine monotherapy continued for up to 26-weeks in youth with schizophrenia or bipolar I disorder Open-label study Medically healthy boys and girls with a baseline diagnosis of schizophrenia (ages 13-17 years) or a manic episode of bipolar I disorder (ages 10-17 years) who participated in one of two acute, double-blind, placebo-controlled studies of immediate-release quetiapine Quetiapine was flexibly dosed at 400–800 mg/day, with options to reduce dosing to 200 mg/day based on tolerability Safety and tolerability outcomes assessed from open-label baseline to week 26 included adverse events (AEs), metabolic/laboratory parameters, extrapyramidal symptoms, suicidality, and vital signs The most common AEs reported during the study included somnolence, headache, sedation, weight increase, and vomiting. 4
PICO: Among children and adolescents aged 10-17 diagnosed with a manic episode of bipolar I disorder, what adverse events will quetiapine dosed at 400–800 mg/day cause compared to patients who do not receive the medication?
Masi, G., Pisano, S., Pfanner, C., Milone, A., & Manfredi, A. (2013) To assess the efficacy of quetiapine monotherapy in adolescents with BD comorbid with conduct disorder (CD) Non-randomized non-controlled study 40 adolescents (24 males and 16 females, age range 12-18 years, mean age 14.9±2.0 years), diagnosed with bipolar disorder comorbid with Conduct Disorder Quetiapine monotherapy (mean final dose 258±124 mg/day, range 100–600 mg/day) Severity of the illness assessed by means of the CGI-S and CGI-I scores; functional impairment assessed with the C-GAS. The majority of participants showed improvements in the score by more than 30 percent. 3
PICOT: Among adolescents who have both bipolar disorder and conduct disorder, can quetiapine monotherapy decrease the severity of the illness compared to those who do not receive the medication within a period of three months?
Habibi, N., Dodangi, N., & Nazeri, A. (2017) To compare the efficacy and tolerability of the combination of lithium and quetiapine with lithium and risperidone in the treatment of manic or mixed episodes in children and adolescents Randomized control trial Thirty patients (aged 10-18 years) who were hospitalized for a manic or mixed episode Random treatment with lithium (with the usual dose to achieve blood levels 0.8-1) and quetiapine (400-600 mg per day) or risperidone (0.5-6 mg per day) Mean decrease in Young Mania Rating Scale (YMRS) score The reduction in YMRS scores was similar in both groups 3
PICOT: In patients aged 10-18 hospitalized for a manic or mixed episode, will lithium plus quetiapine compared to lithium plus risperidone promote the mean decrease in YMRS score within a period of three months?
Suttajit, S., Srisurapanont, M., Maneeton, N., & Maneeton, B. (2014) To systematically review the efficacy and the tolerability of quetiapine, either as monotherapy or combination therapy, for acute bipolar depression Systematic review and meta-analysis People with bipolar I or II disorder who currently had a major depressive episode, irrespective of the diagnostic criteria used, age, ethnicity, and sex Quetiapine, as monotherapy or combination therapy, was investigated in comparison with placebo or other treatments. There was no restriction in the dose, dosage form, and frequency of treatment. Change in scores of depression rating scales (Montgomery-Asberg Depression Rating Scale [MADRS] and Children’s Depression Rating Scale, Revised [(CDRS-R]) Compared with placebo, quetiapine had higher incidence rates of extrapyramidal side effects, sedation, somnolence, dizziness, fatigue, constipation, dry mouth, increased appetite, and weight gain but lower risks of treatment-emergent mania and headache. 3
PICO: Among people with bipolar disorder, will quetiapine (as monotherapy or combined with other medications) compared to placebo improve the scores of depression rating scales?