Studies Of Psychological Treatments In Bipolar Disorders

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Early Treatment Studies

There is a large literature of individual case studies on the use of a variety of psychological therapies in BP. The benefits to individuals with BP described in these papers led to a number of open studies and case series. Between 1960 and 1998 there were 32 published papers describing the combined use of psychological and pharmacological treatments in BP. However, the majority were small-scale studies, with an average sample size of about 25. The combined sample size for all studies was just over 1 000 participants, of which about 75 % received the experimental or novel psychological treatment. The majority of the papers addressed group (n = 14) or family approaches (n = 13), with only 15 % of papers reporting on individual therapy. Most importantly, less than half of all studies (only 13) were randomized controlled trials. The studies also had many methodological limitations. However, it was clear in many of these studies that those receiving adjunctive psychological treatments had better subjective and objective clinical and social outcomes than those receiving usual treatments (comprising mainly of mood stabilizers and outpatient support) and that many of these differences reached statistical significance (for a review see Scott, 1995). These encouraging results facilitated the development of randomized controlled trials of more targeted interventions that primarily focused on the issue of BP relapse.

In the last five years, interest in psychological interventions in BP has increased dramatically with about 20 randomized controlled trials under way in the US, UK and Europe. Given the current emphasis on the use of brief evidence-based therapies in clinical guidelines for the treatment of unipolar disorders, it is not surprising that the new treatment trials for BP have focussed on psychoeducational models, the three most well-researched manu-alized psychological approaches - interpersonal social rhythms therapy (IPSRT), cognitive therapy (CT) and family focused therapy (FFT) - or techniques derived directly from these manualized therapies. The latter are used primarily to improve medication adherence or to teach recognition of prodromes and relapse prevention techniques.

Key Randomized Treatment Trials Brief Technique-driven Interventions

There are two randomized controlled trials of brief six- to 12-session interventions delivered on an individual basis to persons with BP. Each study compared the experimental intervention with a treatment-as-usual condition (usually medication plus outpatient support) and each study followed up participants for at least 12 months. Cochran (1984) undertook a small trial that compared 28 clients who were randomly assigned to standard clinical care alone or standard clinical care plus a six-session intervention that used cognitive and behavioural techniques to improve medication adherence. Following treatment, enhanced lithium adherence was reported in the intervention group with only three patients (21 %) discontinuing medication as compared with eight patients (57 %) in the group receiving standard clinical care alone. There were also fewer hospitalizations in the group receiving CT (two versus eight). Unfortunately no information was available on the nature of any affective relapses.

Perry et al. (1999) recruited 69 participants at high risk of further relapse of BP who were in regular contact with mental health services in the UK. Individuals were randomly assigned to usual treatment or to usual treatment plus six to 12 sessions of cognitive and behavioural techniques that helped individuals to identify and manage early warning signs of relapse. The problem-solving strategies included identification of high-risk situations as well as prodromal symptoms (the relapse signature) and taught clients to self-medicate and to access mental health professionals at the earliest possible time to try to avert the development of full-blown episodes. Over 18 months, the results demonstrated that, in comparison to the control group, the intervention group had significantly fewer manic relapses (27 % versus 57 %), significantly fewer days in hospital, significantly longer time to first manic relapse (65 weeks versus 17 weeks) and higher levels of social functioning and better work performance. However, there was no effect of the adjunctive therapy on rates of depressive relapse.

Group Psychoeducation

Van Gent and colleagues (Van Gent, Vida & Zwart, 1988; Van Gent & Zwart, 1991, 1993) undertook two small-scale trials using a group therapy format for individuals with BP and one trial of psychoeducation for the partners of individuals with BP. The trials were carried out in a clinical setting and would not today meet the rigorous criteria required for randomized trials. Nevertheless, they provide important and useful information that is worthy of review. The first study (Van Gent, Vida & Zwart, 1988) allocated 20 participants with BP to four sessions of 90 minutes of group psychoeducation and 14 other participants to a waiting list control condition (usual treatment). Each group was followed for 15 months. More individuals in the intervention group (75 %) than the control group (29 %) reported significant subjective improvements in self-confidence and those receiving psychoeducation also demonstrated significant improvements in behaviour and social functioning. However, these between-group differences did not extend to mood, anxiety or general symptom ratings. In their second study, Van Gent & Zwart (1991) randomly assigned 15 participants to five sessions of psychoeducation and 20 other participants to 10 sessions of psychoeducation plus psychotherapy. At 15-month follow-up both groups showed improved psychosocial functioning but the only between-group difference was that those receiving the extended intervention demonstrated a greater improvement in their thinking and behaviour as measured on a general symptom checklist. The last study by this group (Van Gent & Zwart, 1993) explored the benefits of providing five structured group sessions for 14 partners of individuals with BP and compared their knowledge of BP, its treatment and psychosocial management strategies over six months with 12 partners who were randomly allocated to a control condition. The study demonstrated that 'partner-only' education sessions led the experimental group to gain and sustain a significantly greater understanding of BP than those allocated to the control group. However, perhaps the most significant finding was that the individuals with BP became significantly more anxious after their partner attended the experimental group without them. This suggests that individuals with BP may benefit from attendance at group psychoeducation sessions but it may be more appropriate to use family sessions if the goal is for both partners and the individual with BP to benefit.

Colom et al. (2003) have undertaken the largest group therapy study so far. It involved randomly assigning 120 participants with BP who were euthymic and receiving medication and standard outpatient follow-up to either 20 sessions of group psychoeducation (approximately eight to 12 individuals per group) or to an unstructured support group. Sessions were 90 minutes in duration and were run by two experienced clinical psychologists. Overall, when the mean number of relapses per subject, the total relapses per group, time to first relapse, length of hospitalization and serum lithium levels were evaluated, there were clear and statistically significant advantages to psychoeducation as compared with the non-directive group. Reductions in depressive relapses were particularly noticeable, and were significantly lower in both the treatment phase (psychoeducation 12 % versus control 31 %) and the follow-up phase (31 % versus 71 %). Furthermore, there was a similar significant reduction in relapse rates into hypomania, and the same trend that sometimes reached significance for manic and mixed states.

Family or Couples Therapy

Four small randomized trials all identified that family therapy may be an important adjunct to pharmacotherapy in BP. Honig et al. (1997) demonstrated that six sessions of a multi-family psychoeducational intervention (n = 23) produced a non-significantly greater reduction in expressed emotion in the experimental as compared to the waiting-list control group (n = 23). Van Gent, Vogtlander & Vrendendaal (1998) compared 'couples psycho-education' (n = 14) with usual treatment (n = 12) and found that those couples receiving the active intervention showed greater knowledge of BP and its treatment and improved coping skills at the end of the psychoeducation sessions and at six month follow-up. Glick et al.

(1994) studied 50 inpatients of whom 19 had been admitted following a BP relapse. They demonstrated that those randomly allocated to additional family therapy (n = 12) showed significant improvements in social and work functioning and family attitudes compared with those who received usual inpatient care alone (n = 7). These gains were particularly noticeable in females with BP and many of the immediate benefits associated with family therapy were maintained at 18-month follow-up (Haas, Glick & Clarkin, 1988). Clarkin etal. (1990) randomly assigned 42 outpatients to 11 months of standard treatment (n = 23) or standard treatment plus 25 sessions of 'couples therapy' (n = 19). Unfortunately the analysis was restricted to 33 treatment completers (couples therapy 18; control treatment 15). Receipt of a course of 'couples therapy' was associated with significantly higher levels of social adjustment and medication adherence compared with the control group, although there were no differences in overall symptom levels in the groups.

Miklowitz et al. (2000) undertook the largest trial of family therapy using their 20-session FFT model. They randomly allocated 101 participants with BP who were receiving usual treatment to FFT (n = 31) or to case management (n = 70), which comprised two sessions of family psychoeducation and crisis intervention as required. Over a 12-month period, individuals receiving FFT plus usual treatment as compared to case management plus usual treatment survived significantly longer in the community without relapsing (71 % versus 47 %) and showed significantly greater reductions in symptom levels. However, further analysis demonstrated that these benefits were limited to depression and there was no specific reduction in manic relapses or symptoms. Overall, the benefits of FFT were most striking in individuals living in a high expressed-emotion environment.

Rea et al. (2003) randomly allocated 53 persons with a recent admission with mania to 21 sessions of FFT (n = 28) or 21 sessions of individual support and problem-solving treatment. The active treatment phase was nine months and individuals were followed up for a further 15 months post-therapy. The groups did not differ significantly in likelihood of a first relapse, and in the first year 52 % of those receiving individual treatment and 46 % of those receiving FFT experienced a BD episode. However, the respective relapse rates during the second year were 60 % and 28 % and those receiving FFT were also significantly less likely to be re-hospitalized during the follow-up period.

Interpersonal Social Rhythms Therapy (IPSRT)

The IPSRT intervention was one of the first systematic psychological therapies developed specifically for individuals with BP. A randomized treatment trial with a two-year follow-up is under way. Interim reports are available on 82 participants initially allocated to IPSRT or intensive clinical management. The trial has two phases - an acute treatment phase and a maintenance phase - and 50 % of participants in each group remain in the same treatment arm throughout the study while the remaining participants cross over to the other treatment arm (Frank et al., 1999). The key findings so far are that IPSRT does induce more stable social rhythms (Frank et al., 1994). There were no statistically significant between-treatment differences in time to remission but those entering the trial in a major depressive episode showed a significantly shorter time to recovery with IPSRT compared to intensive clinical management (21 weeks versus 40 weeks) (Hlastala et al., 1997). Interestingly, those receiving the same treatment throughout the acute and maintenance phases of the study showed greater reductions in symptoms, suicide attempts and total number of relapses than those who were assigned to the cross-over condition. This suggested that consistency in treatment was more important than type of treatment alone.

Cognitive Therapy

A study by Scott, Garland & Moorhead (2001) examined the effect of 20 sessions of CT in 42 clients with BP. Participants could enter the study during any phase of BP. Clients were initially randomly allocated to the intervention group or to a 'waiting-list' control group who then received CT after a six-month delay. The randomized phase (six months) allowed assessment of the effects of CT plus usual treatment as compared with usual treatment alone. Individuals from both groups who received CT were then monitored for a further 12 months post-CT. At initial assessment, 30 % of participants met criteria for an affective episode: 11 participants met diagnostic criteria for depressive disorder, three for rapid cycling disorder, two for hypomania, and one for a mixed state. As is typical of this client population, 12 participants also met criteria for drug and/or alcohol problems or dependence, two met criteria for other Axis I disorders and about 60 % of the sample met criteria for personality disorder. The results of the randomized controlled phase demonstrated that, compared with participants receiving treatment as usual, those who received additional CT experienced statistically significant improvements in symptom levels, global functioning and work and social adjustment. Data were available from 29 participants who received CT and were followed up for 12 months post-CT. These demonstrated a 60 % reduction in relapse rates in the 18 months after commencing CT as compared with the 18 months prior to receiving CT. Hospitalization rates showed parallel reductions. Scott et al. concluded that CT plus treatment as usual may offer some benefit and is a highly acceptable treatment intervention to about 70 % of clients with BP. This study was the forerunner of a large five-centre trial of treatment as usual versus CT plus treatment as usual. The sample (n = 250) is the largest for a psychological therapy in BP and results will be available in the near future.

Lam et al. (2000) followed up their pilot study (25 participants randomized to CT or to usual treatment) of 12 to 20 sessions of outpatient CT for BP with a large-scale randomized controlled trial (Lam et al., 2003). They randomly allocated 103 participants with BP who were currently euthymic to 'individual CT as an adjunct to mood stabilizing medication' or to 'usual treatment alone' (mood stabilizers plus outpatient support). After controlling for gender and illness history, the intervention group had significantly fewer BP relapses (CT group = 43 %; control group = 75 %), psychiatric admissions (15 % versus 33 %) or total days in episode (about 27 days versus 88 days) over 12 months than the control group. The reduction in total number of episodes comprised significant reductions in major depressive (21 % versus 52 %) and manic episodes (17 % versus 31 %) but not mixed episodes. The intervention group also showed significantly greater improvements in social adjustment and better coping strategies for managing prodromal symptoms of mania.

Similarities and Differences in Therapy Outcomes

As shown in Table 18.1, the use of adjunctive therapy leads to significant reductions in relapse rates and symptom levels and significant improvements in social functioning. A number of studies reported improvements in medication adherence in those receiving

Table 18.1 Key randomized controlled trials of psychological therapies for bipolar disorders

Key study

Sample size

Experimental intervention

Main differences in outcome between experimental and control treatments

Perry et al.



= 69

Relapse prevention using cognitive and behavioural strategies

Reduced lengths of hospitalization. Increased time between episodes.

More effective in preventing relapses into MANIA. No effect on depression.

Frank et al.



= 82

Inter-personal social rhythms therapy (IPSRT)

Increased stability of social rhythms. IPSRT more effect on DEPRESSION, with trend towards shorter time to recovery from a major depressive episode. No effect on manic relapse.

Miklowitz et al. (2000)


= 101

Family focussed therapy

Significantly fewer relapses but FFT more effective in reducing DEPRESSION than mania. FFT particularly helpful in families with high levels of expressed emotion.

Lam et al., (2003)


= 103

Cognitive therapy

Significantly fewer episodes of MANIA and DEPRESSION. Improved social functioning. Greater awareness and better coping with manic prodromes.

Colom etal.,



= 120

Group psycho-education

Significantly fewer BP episodes (manic, depressive and mixed), greatest effect on DEPRESSION but also HYPOMANIA.

psychological therapy. However, this alone did not account for the improved outcomes of participants in the intervention group. Some studies also improved the understanding and attitudes of family members toward the individual with BP and the treatment of the disorder.

It is noticeable that therapies sometimes differed in their relative effectiveness in reducing depressive or manic relapses. The reasons for this are not entirely clear but at least two hypotheses can be put forward. First, there may be different active ingredients in the therapy that more successfully tackle the syndrome of depression or mania. Alternatively, it should be noted that the symptoms of manic relapse are qualitatively different from day-to-day experiences whereas depressive prodromes often represent quantitative variations from normal experience; mania also has a longer prodrome than depression (median time approximately three weeks as compared to two weeks) (Jackson, Cavanagh & Scott, 2003). This means that interventions that focus primarily on teaching individuals to recognize early warning symptoms and to make effective interventions (behaviour change or increases in medication) may prevent isolated manic symptoms cascading into a full-blown maniac relapse but may be less effective at identifying and intervening in a timely manner with a depressive prodrome (see Jackson, Cavanagh & Scott, 2003). Interventions that tackle subsyndromal or acute BP depression often require complex multifaceted approaches such as those included in CBT and IPT and already known to be effective in the treatment of unipolar depression.

In summary, although the randomized trials reviewed here are relatively small by comparison to medication trials, there is encouraging evidence for the clinical effectiveness of each key approach. In addition, randomized trials of group therapies targeting comorbid BP and substance misuse (Weiss et al., 2000) or using Bauer et al.'s (1997) 'life goals' programme are nearing completion. Importantly, large-scale studies are now under way on both sides of the Atlantic (the Medical Research Council study in the UK and the STEP-BD project in the US). These trials are likely to answer basic questions about the benefits and limitations of psychological therapies in the acute and maintenance treatment of BP.

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