WikiJournal Preprints/Psychotherapy: An important component of a comprehensive approach to the treatment of bipolar disorder

Bipolar disorder (BD) is a chronic mood disorder associated with debilitating symptoms of mania and depression that can have profound effects on both patients and their caregivers. The presentation of mood episodes in BD varies considerably and is categorized into several subtypes [1]. Bipolar I is characterized by at least one manic episode, which can result in hospitalization. Individuals with Bipolar II will have at least one hypomanic episode and one major depressive episode. Cyclothymic disorder is characterized by at least two years of chronic symptoms of hypomania and depression (or one year in children) that do not meet full threshold criteria for [hypo]manic or depressive episodes. If an individual has clear symptoms of mania, but does not meet criteria for any of the preceding subtypes due to insufficient duration or severity, they may receive a diagnosis of other specified bipolar and related disorder [1].

In addition to mood symptoms, BD is often associated with cognitive and functional impairments that contribute to lower quality of life [2]. The lifetime prevalence of BD in the United States is approximately 4% with similar rates regardless of race, ethnicity, and gender [3, 4]. Globally, it is estimated that BD affects more than 1% of the world’s population [5]. Onset of bipolar spectrum disorders typically begins in adolescence or early adulthood and often goes undiagnosed for several years [6-8]. This is due, in part, to the fact that the initial episode is usually depression, and a [hypo]manic episode may not become evident until later in the course of the illness [9]. Careful assessment of past and current symptoms of mania is crucial to the detection and diagnosis of BD.

Treatment for bipolar disorder typically focuses on reducing the severity of manic and/or depressive symptoms, preventing relapse, and improving overall functioning [10]. Because BD is a chronic disorder, treatment will vary across the course of illness (i.e., acute illness, symptom management, remission maintenance) and often involves a multidisciplinary approach including a combination of psychopharmacological and psychosocial interventions [11, 12]. Generally, treatment for BD is conducted in two phases. Each phase is associated with specific, evidence-based treatment methods, although treatment plans vary depending on the specific needs of the individual [13]. The first phase focuses on acute mood episode management. The goal of treatment in this phase is rapid reduction of mood symptom (manic, hypomanic, or depressive) frequency and severity. Symptoms that are commonly experienced during a manic episode include elevated mood, increased energy, decreased need for sleep, impulsivity, agitation, aggression, and psychosis [14]. Among the symptoms of a depressive episode, suicidal ideation and psychotic features are typically first targeted in acute treatment [15]. Treatment during this acute phase often involves the use of one or more medications such as mood stabilizers, second-generation antipsychotic drugs, and benzodiazepines [16]. The second phase, or maintenance phase, focuses on reducing the risk of relapse [17]. Treatment with medication alone is associated with low rates of remission, high rates of recurrence, the presence of residual symptoms, and significant psychosocial impairment [18]. Thus, the maintenance phase should also include psychosocial interventions to improve medication adherence and overall functioning [17]. When administered in conjunction with pharmacotherapy, psychosocial interventions have been shown to reduce relapse rates by up to 40% [18, 19]. Psychotherapies target certain features of BD that medication cannot, such as interpersonal challenges, acceptance of diagnosis, and identifying early indicators of mood deterioration (Bobo, 2017). Psychotherapy also addresses negative life experiences and stressors that can exacerbate symptoms [10, 17]. Treatment guidelines suggest a combination of both pharmacotherapy and targeted psychosocial intervention to achieve optimal outcomes.

There are several interventions with evidence to support their use with individuals who have BD including psychoeducation, family-focused therapy (FFT), cognitive behavioral therapy (CBT), interpersonal and social rhythm therapy (IPSRT), and dialectical behavior therapy (DBT). Strong support for the benefits of psychotherapy came from The Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD [20]). Across 15 participating states, the study included a randomized controlled clinical trial examining the efficacy of cognitive-behavior therapy (CBT), family-focused therapy (FFT), and interpersonal and social rhythm therapy (IPSRT) for individuals with BD who were on mood stabilizers [20]. Individuals with BD (N=293) were randomly assigned to 30 sessions of FFT, IPRST, CBT, or Collaborative Care (CC; a three-session psychoeducational treatment), and to mood-stabilizing medications—with or without antidepressants. Patients in any of the psychotherapy conditions had higher recovery rates after one year and recovered 110 days faster on average than those in the CC condition. Furthermore, by one year, 77% of patients in FFT, 65% in interpersonal therapy, and 60% in CBT had recovered, compared to 52% of the patients in the CC group [20].

This review aims to summarize the existing treatment approaches for BD across the lifespan with a focus on evidence-based psychotherapies (See Box 1). First, several evidence-based psychotherapies will be described, followed by a brief summary of the role of psychopharmacology and alternative medical treatments.

Psychoeducation
Psychoeducation is intended to provide individuals and their families with knowledge and skills to better understand and effectively manage the symptoms of BD, as well as alleviate associated psychosocial impairments. Although psychoeducation may be administered in various formats, all modalities share a common target of educating individuals and/or families on the symptoms of BD and their subsequent impact on the individual and their relationships [21]. By addressing issues commonly experienced as a consequence of BD, individuals with BD can better understand how to manage their symptoms and subsequently improve their social functioning and overall quality of life [10].

Psychoeducation has more support than any other psychosocial intervention for BD, particularly regarding its effectiveness in preventing future occurrence of manic episodes [17, 22-24]. Due to the important role it plays in achieving positive outcomes, all evidence-based psychotherapies for BD include some element of psychoeducation. Here we describe it in its standalone form, but its themes appear throughout all therapies described in this review.

Generally, psychoeducation involves multiple sessions that take place over the span of several months, either individually or with the individual and their family. In these sessions, education is provided on how to play an active role in one’s treatment while maintaining positive interpersonal relationships [21]. These sessions address common issues associated with BD such as mood instability, nonadherence to medication, and psychosocial impairments. Sessions generally start by promoting an understanding of the illness and associated symptoms. Individuals learn how to identify prodromal symptoms that precede the onset of a full episode, as well as the symptoms of both manic and depressive episodes. As they learn to detect early warning signs of mood episodes, individuals can implement strategies for preventing progression into full mood episodes or relapse [21]. They are encouraged to work with their provider to develop concrete strategies for coping with symptoms, avoiding triggers, and resolving negative interpersonal patterns [25]. Additionally, by maintaining stable mood over time, individuals with BD may suffer less from interpersonal conflict [26]. In addition to developing coping strategies, individuals with BD are also encouraged to maintain consistent daily routines and to prioritize good sleep hygiene to reduce mood fluctuations in response to the environment. Psychoeducation will often include life charting [27], which is intended to help the patient recognize patterns of behaviors or activities that exacerbate their mood symptoms. By recognizing those that are detrimental to their mental health, patients can gain motivation to reduce or avoid them altogether. Some examples include substance use, poor sleep hygiene, and medication non-adherence. Substance abuse is a common comorbidity in individuals with BD that can contribute to further health consequences [28]. Life charting allows the patient to monitor their patterns of substance use and subsequently develop a plan to reduce their substance intake, with the help of their provider.

Another important feature of psychoeducation is the promotion of treatment adherence, particularly with medication, as medication has been found to significantly reduce symptom severity and risk of relapse [29]. People with BD frequently discontinue their medication without consulting a psychiatrist, increasing risk for relapse. This can be due to adverse side effects or believing there is no longer a need for the medication, especially when symptoms have improved. Unfortunately, self-discontinuation is often associated with relapse and can lead to poorer response to medication in the future [30-33]. Educating patients about the importance of medication adherence is a primary goal of psychoeducation, and multiple sessions are typically devoted to this issue. Information about types of medication often prescribed for BD, indications for their use, and potential side effects is provided, along with the effects of withdrawal and consequences of self-discontinuation. Ensuring patients understand these consequences can help promote greater treatment adherence.

As mentioned, psychoeducation can be administered in several formats including individual therapy, family-based therapy, group therapy, and online. The variations in these modalities may provide differential benefits to those with BD depending on their specific needs. Below we outline each modality and its unique aspects.

Individual psychoeducation can be advantageous because the education provided can be tailored to be patient and their specific needs. In addition, the patient may feel more at ease discussing their illness than they would in the presence of other people [34]. Although individually-delivered psychoeducation has shown positive results [29], it is generally less effective than family-based or group psychoeducation, likely due to the additional benefits of social support [23].

Group psychoeducation generally involves weekly sessions, each of which highlight a different element of BD [35]. Patients often create a personalized recovery plan as part of treatment and commit to taking medication consistently and developing a regular routine, along with creating an action plan for when they experience symptoms of an impending manic or depressive episode. The benefit of developing these plans with peers is to encourage participation and idea sharing, provide an opportunity to celebrate achievements, and to increase accountability [27]. Group psychoeducation tends to have a lower dropout rate, and has higher levels of overall satisfaction than individual psychoeducation [36]. Its format is also more cost effective, Similar to group psychoeducation, family psychoeducation can be beneficial in supporting both individuals with BD and their families [37]. Family members of patients with BD may also experience difficulties during treatment, rehabilitation, and recovery, such as increased conflict, emotional burnout, and anxiety [38]. Family-based psychoeducation emphasizes the importance of the family’s role in treatment and provides them with skills for helping the patient to maintain stable mood. Family-based psychoeducation with youth may include some sessions where individuals and their caregivers are separated to learn content at the appropriate developmental level before discussing together what they learned. The joint portion of the session is then used to collaboratively select a goal on which to work in the coming week [39].

Family psychoeducation can be administered with the individual family or with a group of families. Fristad and colleagues (2009) developed and tested a form of treatment known as multifamily psychoeducation psychotherapy (MF-PEP) [40]. This intervention combines components of psychoeducation, family systems, and cognitive behavioral therapies. An important feature of MF-PEP is the support families provide one another [40]. MF-PEP has been found to be highly acceptable in youth, parents, and therapists [41] and can be especially beneficial to families with significant impairments in functioning [37].

To make psychoeducation more widely accessible, a few programs have been adapted for online administration [42, 43]. Internet-based psychoeducation can be ideal for individuals who need increased flexibility, privacy, and anonymity [43], and may improve engagement through increased accessibility of services [44]. Moreover, internet psychoeducation programs allow for the patient to self-monitor and continuously assess their mood symptoms and sleep, as well as physical and social functioning. This therapy may not be feasible if the severity of their symptoms preclude them from sustaining treatment on their own, as it requires a high level of self-motivation and concentration anonymity [43].

Across all modalities, the goals of psychoeducation are to educate the patient and family on symptomology, treatment adherence, and coping skills to prevent relapse and psychosocial impairment. Psychoeducation has strong evidence as an adjunctive treatment for BD, but more research is necessary to better understand for whom it is most beneficial and what modifications need to be made to increase benefits [45]. Determining which components are most effective at targeting specific concerns could help further streamline treatment.

Family-Focused Therapy
Family conflicts contribute to exacerbation of mood symptoms in people with BD [46, 47]. Additionally, low warmth from family and poor social support are associated with more intense symptoms in both adults and youth with BD [46]. As such, enhancing patients’ ability to cope with stress, reducing family conflict, and increasing support are primary treatment goals for family-based therapies. Miklowitz and colleagues developed family-focused therapy (FFT) to improve communication, problem solving, and listening skills between the person with BD and their family [48]. FFT usually consists of 21 sessions over nine months following a mood episode (weekly, biweekly, then monthly). However, the number of sessions can vary based on family’s needs, and shorter models have been tested with younger patients [49, 50].

The first six months of treatment focus on psychoeducation and aim to achieve mood stabilization for the patient [47]. During this phase, patients are often symptomatic and functioning at a lower level than before their episode [51]. An important part of this phase is the relapse-prevention drill in which the patients and families are asked to identify times that the patient is at heightened risk for relapse, such as while on vacation or when using alcohol and drugs [47, 52]. This is accomplished by assisting patients and their family members with making sense of the events that led to the acute episode. This in turn allows them to reach a common understanding of likely relapse triggers and develop plans for how the family will react if there are signs of a developing recurrence. Moreover, providers help with adjusting expectations for the patient's and family's functioning during the recovery period [47].

The second phase is communication enhancement training. The exercises in this phase are geared toward resolving family conflict and encouraging behavior change [47]. The patients and family members practice listening to each other, and the patients learns skills to better regulate their emotions [47]. For example, a family member will practice asking another family member to speak in a lower voice. The aim of the phase is to improve communication skills of the patient and family, thereby teaching clear and direct communication of positive and negative feelings [47]. During the problem-solving phase (months 6-9), the patient’s symptoms have typically remitted and sessions occur less frequently [27, 53]. The patient and their family talk about how the illness has affected their lives and aim to identify unproductive cycles of family interaction. Families also agree on the definition of a problem, brainstorm several possible solutions, weigh the benefits and disadvantages of each proposed solution, and then decide on the solution. Once the solution is decided, the family then implements this plan and checks in with the therapist on how the solution and implementation is working. The first problems discussed are typically simpler in nature, such as where to go for vacation; as the family becomes more successful in problem solving, the sessions move to more complex, emotional challenges [47]. The last few sessions of FFT are held monthly and aimed at reviewing treatment progress and termination. By reviewing the treatment, the family strengthens the gains made during the previous nine months. If necessary, more sessions may be scheduled. In FFT for adolescents, the approach is similar with the same 21 session format, but it also includes a curriculum and skills instruction targeted at the particular traits and behavioral issues common among adolescents [54], including rapid mood shifts, extreme oppositionality, sleep/wake cycle disruptions, and elevated levels of family tension. Furthermore, disorders that may be comorbid in teens—such as attention deficit hyperactivity, anxiety, and conduct disorders—can also be addressed. An important aspect of FFT for adolescents is distinguishing the boundaries between bipolar symptoms and the normal emotional turmoil of adolescence for teenagers and their families [47]. Treatment sessions also provide techniques to parents for fostering their teen's healthy development through developmentally appropriate activities [47].

FFT has a positive impact on the stabilization of mood disorder symptoms, particularly depression [55]. A study examined a nine month, 21-session FFT intervention and found that FFT with medication was associated with lower rates of relapse and longer periods of wellness over a two year period, compared to crisis management and medication [46]. Additionally, FFT is associated with improved depression and mania symptoms and lower hospitalization rates over two years of follow-up [55]. FFT also tends to increase familial prosocial behaviors, such as being more likely to smile at each other, nodding when others spoke, and leaning into each other when speaking [56, 57].

FFT has also been evaluated as a treatment for adolescents with BD [58-60] and adolescents at high risk for BD due to symptoms of mania [60-62] or family history of BD [63]. Adolescents with BD who participate in FFT tend to see their symptoms remit more quickly and spend more time well than those who participate in brief psychoeducation [59, 60]. Similarly, at-risk adolescents achieve remission of mile symptoms faster and stay well longer than those receiving a comparison intervention.

Cognitive Behavioral Therapy
Cognitive behavioral therapy (CBT) for BD is based on the theory that an individual’s thoughts, feelings, and actions are connected, and that changes in mood and cognitive processes during affective episodes influence behavior (and vice versa). The main goals of CBT for BD are to identify and change maladaptive thoughts, attitudes, and behaviors that cause or worsen symptoms. CBT for BD uses structured exercises (e.g. thought records, mood diaries, activity scheduling) to identify and modify automatic negative thoughts and encourage mood-enhancing behaviors [18]. CBT for BD includes four important concepts in its framework: providing psychoeducation, teaching coping strategies for prodromal symptoms, planning activities to regulate sleep schedules and other daily routines, and dealing with long term vulnerabilities [64]. Through psychoeducation and targeted skills learning, CBT decreases risk for relapse and improves depressive symptoms, mania severity, and psychosocial functioning [65]. CBT for BD is similar to CBT approaches for other mental health conditions, but requires some modifications. For instance, behavior activation is a technique used for depression in CBT that focuses on increasing positive reinforcement achieved through activities. However, people with BD may be more sensitive to both reward and punishment and could become “too activated” and at risk for [hypo]mania. Individual CBT for adults with BD is effective at improving mood symptoms and psychosocial functioning when compared to standard care for people with BD [65, 71]. CBT also lowers overall healthcare costs as people who receive CBT tend to seek fewer other services [72].

Individual CBT is typically conducted in 20 sessions across three stages [66]. The first stage focuses on psychoeducation and medication management. Patients learn problem-solving skills, how to limit mood swings, and the importance of establishing a daily routine [66]. Treatment often starts with the development of a detailed illness history. The concept of a diathesis-stress model is introduced, which states that bipolar disorder has a strong biological component that can be triggered or exacerbated by stress [66]. Additionally, the patient learns that thoughts, emotions, and behaviors affect each other, and that modifying one will influence the others. Patients are asked to complete a measure of their mood, general mental state, and answer a few questions on medication at each session. The position of homework is addressed in this context, as well as the importance of the patient's active involvement in this process in order to achieve the best possible therapeutic outcome [66]. The patient also develops an initial list of goals for treatment and address possible challenges around the achievement of these goals.

In the second stage, the patient is taught a wide range of cognitive techniques such as activity schedules, thought monitoring, thought challenging, behavioral experiments, dysfunctional assumptions, detection of early warning signs, and medication compliance. These activities provide cognitive behavioral skills for the patients to recognize prodromal symptoms and identify effective coping strategies [66, 67]. The activity schedule is a technique in which the patient monitors their schedule for 24 hours and identifies natural variations in mood and sleep patterns [66]. The patient also uses the thought challenge and dysfunctional assumptions techniques to review their thought monitoring and challenge maladaptive thoughts. Behavioral experiments are assigned and reviewed weekly with the therapist. Behavioral experiments are planned experiential activities that the patient does to gather information and test the validity of their beliefs, then test out more adaptive beliefs [68]. Furthermore, techniques to identify early warning signs include using information from the patient’s self-monitoring to understand signs that may be indicative of manic or depressive prodromal states for the patient. Patients also identify their warning signs for the prodromal phase of their episodes and develop action plans to address these warning signs and avoid relapse [66].

The third stage reviews the importance of sleep, diet and routine, along with the risks of sensation-seeking behavior and substance abuse. Sleep schedules are very important for people with BD, as disruptions in circadian rhythms increase the risk of mood episode onset [69]. Patients are taught how to maintain a good social routine in order to avoid disrupting their circadian rhythms [70]. To accomplish this, patients are taught behavioral skills to establish routines, such as activity planning [66]. Also, the third stage focuses on maintaining the cognitive and behavioral techniques mentioned in stage two. The patient reviews past episodes and identifies triggers and vulnerabilities to events, such as extreme goal-oriented behavior that results in stress and relapse on a regular basis [66]. The sessions discuss how the techniques have been applied, how well they have been implemented in the patient’s life, and how the patient can continue them and prevent relapse [66].

Child- and family-focused CBT
Child- and family-focused cognitive behavioral therapy (CFF-CBT) was developed to meet the specific needs of youth with BD. it was built on three principles: 1) BD in youth is unique and presents differently than it does in adult populations; 2) youth with BD, as compared to youth without BD, show different neural activity patterns such as excessive reactivity of the amygdala and underactivity in the frontal cortex, both of which are related to symptoms associated with BD in youth (i.e. emotional reactivity, poor problem solving); 3) symptoms of BD in youth are exacerbated by their environment [73]. Given these three distinguishing factors, treatment for youth often requires adaptation of treatments found to be effective in adults [74]. CFF-CBT combines several forms of therapy such as psychoeducation, mindfulness-based therapy, and interpersonal/family therapy to address the unique needs of children with BD.

The components of CFF-CBT can be easily remembered with the acronym “RAINBOW:” Routine, Affect regulation, “I can do it!”, No negative thoughts/Live in the now, Be a good friend/Balanced Lifestyle, “Oh how do we solve this problem?”, and “Ways to find support.” For youth with BD, changes in routine can lead to intensified mood dysregulation. For this reason, the “Routines” stage is focused on establishing a simple and predictable routine that is intended to aid mood regulation and reduce symptom severity. Additionally, youth with BD frequently experience difficulties regulating their emotions. Thus, the goal of the Affect Regulation aspect of CFF-CBT is to teach behavioral management and coping skills that youth can use to help regulate their emotions. In the following stage, “I can do it!,” the provider’s primary goal is to instill a sense of confidence in both youth and their parents that they have the ability to cope with the disorder. A stronger sense of self-efficacy may contribute to stopping or slowing the recurrence of mood episodes; therefore, it is essential that this aspect of BD is specifically targeted [73]. Similarly, youth are supported in learning how to decrease negative thinking about themselves and are encouraged to live in the present moment, with reduced catastrophic thinking. “Be A Good Friend/Balanced Lifestyle” is aimed at improving social functioning in youth. Additionally, parents or caregivers may also experience stress and other negative consequences associated with having a child with BD. The Balanced Lifestyle phase of the intervention includes finding ways for parents to re-energize and live a more balanced lifestyle. Families are also taught effective and collaborative problem-solving skills, which can be particularly helpful for youth with BD, as these skills are often impaired in this population. Finally, families are taught how to identify and seek support from their family, school, and community.

CFF-CBT is typically delivered in 12 weekly sessions, each lasting 60-90 minutes. Some sessions focus on the child, some on the parent, and some are family sessions [73]. After they have completed the first 12 weeks, six monthly follow-up sessions serve as a “maintenance phase,” during which providers encourage families to continue using their skills. A crucial factor of CFF-CBT is the active involvement of both the individual with BD and their caregiver(s). At the start of the treatment, the provider begins by explaining to the patient and their family the importance of engagement. The provider facilitates a discussion with the family that allows them to identify and address potential barriers to treatment. The provider also reminds the family that progress comes through practice outside of the session and that everyone must work together for change to occur. To promote improvement outside the therapy sessions, CFF-CBT also involves “homework” that the parent and child are expected to complete each week. Homework may include tasks similar to what adults in CBT would do, like asking the child to keep track of how they are feeling throughout the week [73]. By being mindful of their experiences and emotions throughout the week, the child is practicing the skills learned in therapy sessions and actively engaging in treatment-related tasks.

Participants in a feasibility study of CFF-CBT experienced reduced symptom severity for both mania and depression. Additionally, families stayed engaged in the treatment and reported high satisfaction [50]. In a larger RCT, youth who received CFF-CBT had significantly reduced mania symptoms and reduced parent-reported depression after treatment [73]. These families reported higher satisfaction with all aspects of CFF-CBT treatment and its outcomes as compared to those in the control group who were assigned to a therapist in a general psychiatry clinic. Youth also demonstrated improved global functioning and reported having meaningful social relationships, improved functioning at home, and fewer behavioral problems [73]. Compared to families receiving treatment as usual, CFF-CBT families were less likely to drop out and attended more sessions.

Interpersonal and social rhythm therapy
Interpersonal and social rhythm therapy (IPSRT) is a psychosocial intervention that draws upon the principles of interpersonal psychotherapy and aims to strengthen daily routines and associated social rhythms [75-77]. This approach is based on findings that disruptions of daily routine affect the circadian rhythm, which is the body’s internal process of regulating the sleep-wake cycle [78-80]. Changes in the circadian rhythm induce multiple responses in the body including emotional (e.g. irritability, anxiety, depressed mood), cognitive (e.g. reduced concentration, decreased memory, reduced decision making), and somatic (e.g. drowsiness, metabolic abnormalities, reduced immunity), all of which have major health consequences [81]. Typically, these responses are brief or transient, and balance to these systems is restored. However, individuals with BD can be especially sensitive to changes in their daily routines [82, 83]. When individuals who are vulnerable to mood disorders experience disrupted circadian rhythms, their emotional and cognitive stability can be compromised leading to mood episodes [76, 84]. A primary way by which stable circadian function is maintained is through sustained daily routines. Other people can be important to the maintenance of daily routines – sharing meals and activities are helpful ways to establish a consistent schedule. Thus, IPSRT aims to stabilize social rhythms and improve interpersonal problems that contribute to the onset and recurrence of mood episodes. IPSRT has been adapted for individuals with bipolar II disorder [85], for adolescents diagnosed with BD (IPSRT-A) [86], and for youth at risk for BD [87].

With these aims in mind, IPSRT typically proceeds in three phases. The initial phase involves a review of the patient’s mental health history to understand associations between social routine disruptions, interpersonal problems, and affective episodes. As the quality of their relationships is ascertained, an interpersonal problem area is identified as a target of treatment. Problem areas include grief, role dispute, role transition, and interpersonal deficits. Overall, the initial phase works towards assessing the history and severity of the patient’s disorder, along with identifying the treatment focus and establishing rapport.

The intermediate phase focuses on stabilizing daily rhythms, developing strategies to manage symptoms, and resolving the identified interpersonal problem area. A behavioral approach is used with social rhythm strategies that encourage regularity and stability, such as with establishing proper sleep hygiene and maintaining regular mealtimes [76]. This may involve significant life changes, such as switching from a night shift to day shift for work [77]. Additionally, medication adherence is encouraged while supporting ways in which to establish a regular schedule, such as using alarms as reminders and daily pillboxes to keep track of which medications to take at certain times [76]. Given the influence that others can have on lifestyle and routine, identifying interpersonal sources of stabilizing and destabilizing influence is important for maintaining the integrity of social rhythms [76, 77]. Interpersonal strategies used during this phase are similar to those used in interpersonal psychotherapy for unipolar depression [88]. Cognitive-behavioral strategies, such as self-monitoring, realistic goal-setting, and task assignment, may also be used to establish regular routines for eating, sleeping, and social activity [77].

The third phase aims to reinforce the techniques learned in treatment and help the patient build confidence to maintain social rhythms and positive interpersonal relationships. This can involve review of early warning signs of episodes and continued monitoring of social rhythms. The final phase involves further reduction in frequency of visits to work towards termination, consolidating treatment gains and reinforcing confidence in the patient to apply learned strategies.

STEP-BD found that although there were no significant differences between the three intensive psychotherapies of CBT, FFT, and IPSRT, patients who received any of the three treatments reported significantly higher year-end recovery rates and shorter times to recovery than those in collaborative care [20, 89]. Similarly, another randomized controlled clinical trial found no significant difference between IPSRT and specialist supportive care on depressive symptoms, social functioning, and mania symptoms [90]. In contrast, the Maintenance Therapies in Bipolar Disorder Study (MTBD) found that IPSRT was associated with greater stability of daily routines and sleep-wake cycles and that increased regularity of daily routines mediated likelihood of recurrence [91]. IPSRT is also efficacious for treating manic, anxiety, and depressive symptoms and is associated with low drop-out [92]. IPSRT has also been implemented in a group therapy format across a continuum of care in inpatient, intensive outpatient, and outpatient settings [93]. Patients who participate in group IPSRT spend significantly less time depressed post-treatment than pre-treatment [94].

An open study of IPSRT-A showed high treatment acceptability and retention with significant improvement in mood and general psychiatric symptoms and global functioning among youth diagnosed with BD [95]. IPSRT-A is considered to be an experimental treatment, as it has yet to be tested in an RCT or at least enough studies to meet possibly efficacious criteria as a treatment for youth with BD [96]. In a pilot study on IPSRT for youth at risk of BD, participants showed improvements in sleep patterns (i.e. less weekend sleeping in and oversleeping) but no change in sleep-wake times during the week and overall mood symptoms [87]. However, 67% of recruited families ultimately declined to participate, which suggests this approach may not be acceptable in this population [87]. As a next step, a pilot randomized trial of IPSRT plus referral for community treatment was conducted with youth of parents with BD [97]. Compared to the referral alone condition, there was no significant difference in mood and psychiatric symptoms or sleep. However, there was a significant improvement in refusal rate (21%) among those contacted about participation over that in the initial open pilot study.

Dialectical behavior therapy
Originally developed by Marsha Linehan to treat suicidal behavior in individuals with borderline personality disorder [98, 99], dialectical behavior therapy (DBT) is another psychosocial intervention that has been effectively used in the treatment of BD. Enhancing dialectical thinking in place of dichotomous thinking promotes acceptance within the context of change towards the overarching goal of developing “a life worth living” [98, 100]. DBT is characterized by its multimodal approach using individual therapy, group skills training, phone coaching, and consultation team [99].

DBT is a comprehensive treatment that includes strategies to approach and resolve complex clinical problems [99]. Behavioral targets include decreasing imminent life-interfering behaviors (e.g. suicide attempts, non-suicidal self-injury), reducing therapy interfering behaviors (e.g. missing sessions, not returning phone calls), decreasing quality-of-life interfering behaviors (e.g. substance dependence, homelessness, chronic unemployment), and increasing skillful behaviors in place of dysfunctional ones (e.g. mindfulness, emotion regulation). Modularity enables flexibility and specificity in the approach used, depending on the affected individual’s clinical presentation [99]. This is especially observed in skills training, a known feature of DBT that aims to replace dysfunctional behaviors with more adaptive ones. With the use of handouts and worksheets, skills are organized into the following modules: mindfulness, interpersonal effectiveness, emotion regulation, and distress tolerance.

As an acceptance-based strategy, mindfulness involves a practice of being able to “become one” with experience [98]. One skill is achieving “wise mind” in which reasonable mind and emotion mind are synthesized together. With increased mindfulness, individuals with BD can become more attuned to their mood shifts and able to take action before a mood episode worsens [101]. Distress tolerance is the capacity to experience and endure negative psychological states. Skills that are taught in this module include distraction using ACCEPTS (Activities, Contributing, Comparisons, Emotions, Pushing Away, Thoughts, Sensations) and physiological change using TIPP (Tip face into cold water, Intense Exercise, Paced Breathing, and Paired Muscle Relaxation). Through these skills, distress tolerance reduces engagement in maladaptive behaviors by increasing the ability to downregulate and tolerate negative emotions [102].

Emotion regulation is a change-based strategy that focuses on ways in which an individual can identify, change, and manage emotional responses. Because emotion dysregulation is a core component of BD [103, 104], targeting emotion regulation can also help reduce other symptoms associated with BD [105, 106]. For example, attention, concentration, and awareness are improved through emotion regulation, which also supports better executive functioning [105]. Moreover, emotion regulation skills such as PLEASE (Treat Physical Illness, Balance Eating, Avoid mood-altering drugs, Balance sleep, and Exercise) help promote maintaining a regular sleep schedule, which is especially important for individuals with bipolar disorder who are vulnerable to circadian rhythm disruptions [82].

Interpersonal effectiveness involves learning how to build and maintain positive relationships while changing or eliminating negative relationships [107]. Patients learn to make requests effectively using DEAR MAN (Describe, Express, Assert, Reinforce, Take Hold of Your Mind, Appear Confident, and Negotiate) and to build relationships using GIVE (Be Gentle, Act Interested, Validate, and Use an Easy Manner). Because social support and positive relationships play an important role in maintaining wellness for most adults with BD, these skills can have a strong impact [108].

DBT has been adapted to treat BD in adolescents [109]. Modifications include making the intervention less intensive, reducing the number of skills taught, incorporating family members into the treatment, simplifying the language used in handouts and skills training didactics, and adding an optional 12-week follow-up Patient Consultation Group [109, 110]. With these adaptations, DBT effectively addresses suicidal behavior [111], interpersonal deficits [112], and poor family and peer relationships in this population [113].

DBT has been successfully adapted into group skills training as a standalone treatment that significantly improved psychological well-being and decreased emotional reactivity in individuals with BD [106]. A randomized controlled, pilot study also found that those who were in a DBT-based psychoeducational group showed a trend towards reduced depressive symptoms and significant improvement in emergency room visits and mental health-related admissions in the following six months, compared to those who were in the waitlist control group [107].

In an open pilot trial for adolescents, DBT was feasible and acceptable to 90% of patients [114]. This study also showed significant improvement in suicidality, non-suicidal self-injury, emotional dysregulation, and depressive symptoms from pre-treatment to post-treatment. DBT can be effectively implemented in acute-care child and adolescent psychiatric inpatient units [115]. Similarly, a pilot randomized trial found that adolescents with BD who received DBT showed significant improvement in depressive symptoms and suicidal ideation, compared to treatment as usual [116].

Mindfulness Practice
Mindfulness involves attending to the present moment, noticing thoughts and feelings without judgment or intent to change them, and using breathwork to bring conscious awareness to the body [117]. Over the years, it has been implemented in psychological interventions, such as mindfulness-based cognitive therapy [118] and mindfulness-based stress reduction [119]. Mindfulness-based cognitive therapy (MBCT) has also been used in the treatment of BD with evidence that it can help reduce depressive and hypomanic or manic mood symptoms, while increasing emotion regulation, well-being, and positive affect [120]. Although there are other mindfulness-based practices, MBCT is the most studied. A systematic review found that MBCT is a promising treatment in conjunction with pharmacotherapy for BD [121]. Specifically, it is associated with improvements in cognitive functioning and emotion regulation, as well as reduction in symptoms of anxiety, depression, and mania. These treatment gains were maintained at 12-month follow-up when mindfulness was practiced for at least three days per week or booster sessions were included. However, there is not support for MBCT as a treatment for manic symptoms or as a preventive intervention against future episodes for people with BD [121]. The review also noted the need for standardized guidelines on implementing mindfulness-based treatments for patients with BD, as there is little consistency in the literature regarding the content, frequency, or duration of the mindfulness intervention.

Psychopharmacology
Treatment for youth and adults with BD involves the use of one or more psychopharmacological interventions to reduce symptom severity and stabilize mood [11]. Specific medications are selected based on factors such as symptom severity, the nature of symptoms (e.g., presence of psychosis), treatment history, and medical comorbidities. Some symptoms can be managed successfully using one type of medication, while others require the use of multiple agents. There are several different classifications of medication that can be effective in adults with BD including mood stabilizers, antipsychotic drugs, and benzodiazepines [17]. In youth aged 12 years and older, the use of some second-generation antipsychotics (risperidone, aripiprazole, and quetiapine, olanzapine, and asenapine; https://www.accessdata.fda.gov/scripts/cder/daf/), lithium, as well as olanzapine and fluoxetine combined, have been approved for use by the Food and Drug Administration for treatment of BD symptoms [11].

Mood stabilizers
Mood stabilizers are commonly used to address acute symptoms of mania [17]. Lithium is a common mood stabilizer to treat acute mania and psychosis in adults and is often combined with other mood stabilizers or antipsychotics [15]. Lithium’s effectiveness in managing acute mania, both on its own and in conjunction with divalproex, is well-supported [17]. Lithium has also been approved for use in youth aged 12 years and older, and has been found to be reasonably effective in reducing symptoms of mania [122]. While negative side effects of lithium include nausea, headache, and fatigue, it has been found to be more tolerable as compared to some second-generation antipsychotics (SGAs) [123]. Mood stabilizers are also commonly prescribed for long term maintenance and have been found to be effective at preventing relapse [124].

Antipsychotics
SGAs have substantial support for their efficacy in the use of treating acute mania and/or mixed episodes and have been approved for use in adults and youth aged 10-17 [11, 17, 19]. Risperidone, olanzapine, and quetiapine should be considered to treat acute agitation in adults [17]. Other SGAs such as aripiprazole, asenapine, cariprazine, and ziprasidone are effective for treating acute mania and rapid cycling in adults with BD [15]. Older antipsychotics, such as haloperidol, have also been found to be effective in treating acute mania in adults [17]. There is evidence that SGAs are superior to mood stabilizers in the treatment of mania in youth with BD [123, 125]. However, although SGAs are often effective in treating mood symptoms, they are also associated with myriad adverse effects including weight gain and metabolic syndrome [123]. These side effects must be considered carefully, in conjunction with treatment benefits, when considering SGAs.

Anticonvulsants
Anticonvulsants can also be used to treat mood episodes; however, their effectiveness is not as well supported as that of mood stabilizers [15]. Anticonvulsants such as Divalproex and Carbamazepine can be used to stabilize mood in adults, but their use has not been approved for youth [11]. There is evidence that prescribing anticonvulsants in combination with SGAs, may more effectively target both manic and depressive symptoms [17]. Generally, anticonvulsants are not prescribed as a standalone first-line treatment unless other medications are contraindicated [15].

Antidepressants
The use of antidepressants in the treatment of BD is controversial. Some clinicians avoid prescribing antidepressants to people with BD (or at high risk) due to concern about antidepressant-coincident mania; data on the topic are mixed and treatment guidelines typically recommend prescribing a mood stabilizer with the antidepressant [126-128].

Medications that effectively treat an individual’s acute symptoms are generally continued in an effort to avoid relapse in the maintenance phase [15]. However, many medications are associated with physical side effects that should be monitored closely, so that the benefits of the medication can be appropriately weighed against the consequences [15].

Electroconvulsive therapy
Electroconvulsive therapy (ECT) is a medical procedure in which brief, generalized seizures are induced through electric currents administered to the brain while the patient is under anesthesia [129]. ECT has been established as a safe and effective option for people with BD symptoms that do not respond to other forms of treatment during both the acute [130-133], and maintenance phases [134, 135]. ECT can effectively treat multiple mood states including bipolar depression, mixed symptoms, mania, and catatonic features [136, 137]. People can experience memory deficits following ECT [138, 139] and many feel nervous about undergoing “shock therapy,” which has limited its use despite being the recommended intervention for treatment refractory cases of BD [140]

Transcranial magnetic stimulation
Transcranial magnetic stimulation (TMS) is a therapeutic intervention that involves the application of magnetic pulses on hyperactive or hypoactive cortical brain regions to modulate brain networks, resulting in neural activation changes [141]. Although multiple systematic reviews have found that TMS is a promising approach for treatment refractory symptoms in patients with BD [142, 143], the results of individual trials are mixed [144-146]. Although it may be less effective than ECT, there are a few advantages of TMS, including the lack of memory or other cognitive impairments [146, 147] and other adverse events or induction of mania [145, 146, 148, 149]. The use of TMS as a treatment for mania has not yet been evaluated.

Chronotherapy
Due to the association of BD with circadian function and evidence of dysregulation of melatonin secretion and sleep-wake cycles during mood episodes [150], a number of chronotherapeutic interventions have been developed and tested in people with BD [82]. These include bright light therapy, dark therapy, sleep deprivation or wake therapy-based treatments, melatonergic agonists, and behavioral interventions such as interpersonal and social rhythm therapy and cognitive behavioral therapy for insomnia adapted to BD [151]. Light therapy is the use of bright white light or dawn simulation to entrain the circadian rhythm by suppressing the release of melatonin and lengthening the photoperiod [152]. Bright light therapy is particularly indicated for people whose mood episodes have a seasonal pattern [152-155]. Light therapy is consistently associated with improvement in symptoms of bipolar depression [82, 156, 157]. However, the timing, duration, and intensity of the light exposure are important to balance the benefits with potential risks [152]. One such risk is the induction of mania [158], although data are mixed in terms of the severity of this risk [159, 160]. In some cases, bright light therapy has been used in conjunction with sleep deprivation [150]. Sleep deprivation often helps ameliorate symptoms of depression [161, 162]. Unfortunately, it is not a practical intervention for most because rapid relapse is common after the first recovery sleep [163], and sleep loss is associated with the onset of mania [164].

Lifestyle interventions
While psychopharmacology and psychotherapy should be prioritized as first line treatments for BD, there are several lifestyle considerations that can also help. As described above, getting consistent sleep and maintaining a routine are very important to mood stability; healthy diet, exercise, and the use of some dietary supplements may also be beneficial. Individuals with BD are at high risk for conditions such as obesity and cardiovascular disease (CVD) [165-167]. This association has led some to postulate that BD is, at least in part, caused by CVD [165, 167-169]. Based on this theory, regular physical activity and maintaining a healthy diet are recommended in order to combat CVD and its sequelae [170]. Although research investigating the exact benefits of diet and exercise for people with BD is limited, there is some evidence to support exercise and diet as interventions in this population [171]. Yoga is one form of exercise that has been investigated as a treatment for people with mental health disorders and is associated with improved symptoms of depression [172]. In a small pilot trial of people with BD who practiced yoga, participants reported emotional, cognitive, and physical benefits [173]. Despite promising preliminary findings, more research is needed to determine the feasibility, practicality, and efficacy of yoga therapies for those who suffer from mood disorders.

Although dietary supplements are not sufficient as standalone treatments for BD, there is some evidence that they may be beneficial for individuals with BD (or other psychiatric disorders)  in conjunction with psychopharmacology [174]. The American Psychological Association (APA) recommends the use of Omega-3 fatty acids for depressive disorders, impulse-control disorders, and psychotic disorders. Omega-3 fatty acids improve promoting heart health and metabolism, which may be particularly beneficial for individuals with BD who are at an increased risk for conditions such as obesity and CVD [175]. The literature on the benefits of omega-3 fatty acids for individuals with BD is currently limited to depressive symptoms [39, 176-178]. The benefits of other supplements, such as multi-nutrients, have also been evaluated. In a small open label study of micronutrients, youth with BD experienced an improvement in their depressive symptoms, on average [179]. Research on vitamins and other supplements is very limited and lacks randomized trials from which stronger support could be gleaned. Larger, more rigorous investigations are necessary to determine whether these may be beneficial when used in conjunction with pharmacological and psychosocial treatment methods [180].

Discussion
Bipolar disorder impairs multiple domains functioning and affects more than 1% of the world's population [2]. Its onset during the important developmental period of adolescence and often long delays before accurate diagnosis and treatment contribute to its significant burden. Individuals with BD have benefitted from pharmacological treatments since lithium started being prescribed the 1950s, and a number of other classes of drugs have since been approved to treat BD. More recently, psychotherapy treatments have been developed to help maintain stable mood and improve quality in people with BD [18]. Unfortunately, despite these advancements, partial or no response to traditional treatments is common [181]. Among the participants in the STEP-BD trial, the rate of recovery was less than 60%, with almost 50% of the participants relapsing during the 2-year follow-up period [182].

Barriers to Treatment
Combining psychotherapy and pharmacotherapy to stabilize mood episodes and prevent future ones is now accepted as the preferred treatment approach [10, 18]. However, there exist several barriers to accessing these treatments. Many individuals with BD live in rural or low-income communities, where access to mental health care is limited and access to evidence-based psychosocial interventions for BD may be nonexistent [183]. One way to help address this limitation is to train providers in under-served communities to deliver evidence-based treatment for BD. Unfortunately, many providers are not aware of which treatments have support for their use in people with BD and may not be interested in learning new approaches [184]. Even when there are providers trained in appropriate treatment approaches, many treatment options are unaffordable for the individuals who could benefit from their use. Disseminating information about the benefits of evidence-based treatment and training providers who work in school- or community-based treatment facilities, which serve low-income people, could greatly expand access and help address the significant public health burden of BD. Technology also holds promise as a way by which to increase access to evidence-based care [185, 186]. As people become increasingly familiar with technology (e.g., smartphone apps, telehealth), its potential as a mental health care tool grows. For example, people in rural or otherwise underserved communities may be able to access treatment with trained providers who live elsewhere through telepsychiatry or people who cannot attend weekly psychotherapy maybe be able to augment less frequent appointments with an app that provides additional therapeutic content. Technology can also facilitate peer support, which is associated with improved outcomes [187] and can help people with BD to better manage their illness with tools to help with the identification of warning signs and triggers, practicing better sleep hygiene, improving medication adherence, and increasing social support [188-190]. Technology may also be useful for identifying diagnostic markers of BD (e.g., unusual sleep/wake patterns or changes in energy expenditure [191-193] and for tracking symptoms over time to quickly identify and address any worsening of symptoms.

Another challenge is the fact that not all people with BD respond well to the available medications. The symptoms of bipolar depression, in particular, may not fully remit with treatment [169]. Although mood stabilizers, both alone and in conjunction with antidepressant medication, can help, there is a need for more effective agents. If there were medications that fully ameliorated symptoms, people with BD might be more inclined to stick with their treatment regimen. As it is, patients often experience ongoing mood symptoms and significant medication side effects, which hamper adherence. The development of new psychotropic agents to treat BD is limited by the relatively low prevalence of the illness and the complications related to the varying mood states patients experience [194]. However, the public health burden is high and there would be significant benefit to individuals and to the community if people with BD could more consistently achieve remission. Research to develop and evaluate medications for youth with BD is also an important next step. Despite the fact that adolescence is the period during which most people with BD first experience symptoms [9], relatively few medications are FDA-approved to treat BD in youth and little work has been done to systematically test dose and formulation of existing medications to find out what works best in young people. In addition to effectively managing symptoms, it is helpful for youth to have a positive experience with their psychiatric treatment (i.e., understanding the need for medication, experiencing few side effects), as this will increase the likelihood that they stick with their doctor’s recommendations. Because youth can be especially sensitive to concerns about stigma and things that make them different from peers [195, 196], approaching treatment in a respectful way is essential.

Due to inconsistencies in treatment adherence and because BD is an episodic illness, many people with BD will experience a mental health crisis at some point. Unfortunately, these events often result in trips to the emergency department and inpatient hospitalization. Treatment in the ED or an inpatient unit is expensive and disruptive and can lead to additional hardships (e.g., child custody issues, lost work, financial insecurity, embarrassment and stigma). If behavioral health urgent care centers were more widely available, people with BD could receive immediate care without extra consequences [197]. Behavioral health urgent care centers can also help communities by reducing the need for mobile crisis teams, and opening availability for outpatient care [198]. However, these centers tend to be clustered in high income areas, making them less accessible to the people in greatest need [198].

Treatment Considerations
Treatment outcomes may be impacted by cultural factors. Most studies of both pharmaceutical and psychosocial interventions for BD have been conducted in the United States among individuals who are mostly westernized and Caucasian. Culture influences multiple aspects of mental health and its treatment, including symptom manifestation, family understanding, and treatment attitudes [199, 200]. Taking these factors into account when developing and prescribing treatment plans is crucial. However, at this stage, our knowledge about cultural influences on BD is limited [201]. Research to better understand how culture impacts BD is important to reducing barriers treatment, improving assessment accuracy, and educating patients and families about the importance of intervention.

As noted, there are a number of psychosocial interventions that have evidence of effectiveness for people with BD and, on average, they are have similar outcomes [18]. However, little is known about how treatment outcomes may vary by individual or how best to match patients with the treatment most likely to help them [41, 202, 203]. For example, DBT is a treatment that stresses the importance of suicide prevention and targets life-interfering behaviors such as suicide attempts and non-suicidal self-injury. Thus, for an individual with BD who is high-risk for suicide, DBT may be the best option. IPSRT treatment underscores the importance of maintaining regularity and stability in a person’s circadian rhythm and therefore might suit individuals who struggle with sleep disturbance. Investigating how patient characteristics influence treatment response will help ensure the treatment with the best chance of addressing the patient’s primary concerns is administered first [204]. With optimal treatment, many individuals with BD can function well and live independent, fulfilling lives.

The treatments discussed above address the symptoms of BD. However, individuals with BD often have comorbid mental health disorders [169, 205-208]. These comorbid disorders can exacerbate BD symptoms and make it harder to achieve remission. Fully assessing all domains of functioning to identify comorbid disorders [209] and finding the most effective medication combination to treat symptoms is important to helping patients achieve functional wellness [210]. This process can be challenging and increases the likelihood of medication side effects that are unacceptable to the patient; considering the consequences and benefits of each intervention in collaboration with the patient and their family is the best way to develop a treatment approach with which the patient will adhere.

Conclusion
In sum, individuals with BD who receive psychotherapy, whether in a group or individual setting, fare significantly better than those who do not [18]. Randomized controlled trials that compare different evidence-based psychotherapies for BD indicate little difference between the treatments on average [18], but little is known about if/how individual patient characteristics moderate treatment outcomes. Selecting a treatment that most directly targets a patient’s primary treatment goal is a good start. Unfortunately, access to most evidence-based treatments for BD is limited [211]. Expanding the availability of psychosocial interventions and improving pharmaceutical approaches to better target symptoms without significant side effects are crucial next steps to reducing the significant burden BD represents for individuals and society. Greater attention must also be paid to learning which treatment approaches work best for youth and to gaining knowledge about how patient characteristics impact treatment outcomes. As technology and other advances make personalized care a reality for more people, treatment research needs to meet the challenge of identifying what works best for whom and, subsequently, address the gaps that limit some patients’ ability to achieve a good quality of life.

Competing interests
The authors have no competing interests.