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Psychother Psychosom 2007;76:271–277 DOI: 10.1159/000104703

The Treatment of Psychotic Major : Is There a Role for Adjunctive ?

a a b Brandon A. Gaudiano Ivan W. Miller James D. Herbert

a Department of and Human Behavior, Brown Medical School and Butler Hospital, Providence, R.I. , and b Department of Psychology, Drexel University, Philadelphia, Pa., USA

Key Words There are several empirically supported biological and Major depression Cognitive behavior therapy psychosocial treatment options currently available for in- Combined treatments Hospitalized , depression dividuals suffering from major depression. However, de- pression is a heterogeneous condition, and far less re- search has been conducted on the adaptation of treat- Abstract ments for specific diagnostic subtypes. Population studies Background: Psychotic depression is a relatively prevalent estimate that psychotic features (i.e. and/ associated with greater symptom severity, a or ) are present in 14–19% of patients with major poorer course of illness and higher levels of functional im- depression, giving it a lifetime population prevalence of pairment compared with nonpsychotic depression. Sepa- over 2% [1, 2]. The rates tend to be particularly high in rate lines of investigation suggest that various forms of cog- hospitalized depressed patients, with up to 25% meeting nitive-behavioral therapy are efficacious for treating severe criteria for psychotic depression (PD) [3] . In this paper, forms of nonpsychotic depression as well as primary psy- we review the clinical features of PD and present the pre- chotic disorders. However, there currently are no empirically liminary data to date on psychotherapy response in pa- supported specifically designed for treat- tients with PD. We then briefly discuss research and ing psychotic depression. Method: We review the efficacy of treatment implications based on current empirical knowl- current somatic treatments for the disorder and discuss the edge. limited data to date on potentially useful psychotherapeutic approaches. In particular, we describe the clinical improve- ment observed in a subgroup of hospitalized patients with Clinical Features and Course of PD psychotic depression treated with Acceptance and Commit- ment Therapy as part of a larger clinical trial. Results: Pilot Patients with PD can be differentiated from those with results demonstrated that Acceptance and Commitment nonpsychotic depression based on a number of neurobio- Therapy was associated with clinically significant reductions logical and neuropsychological abnormalities, including in acute symptom severity and impairment compared with distinct patterns of structural brain anomalies, hypotha- treatment as usual. Conclusion: The findings suggest that lamic-pituitary-adrenocortical axis activity, patients with psychotic depression can benefit from psycho- and serotonin neurotransmission, and cognitive deficits therapy. Clinical and research recommendations in this area [4–6]. Other clinical characteristics of PD include greater are presented. Copyright © 2007 S. Karger AG, Basel symptom severity, number of attempts, psycho-

© 2007 S. Karger AG, Basel Brandon A. Gaudiano 0033–3190/07/0765–0271$23.50/0 Psychosocial Research Program, Butler Hospital Fax +41 61 306 12 34 345 Blackstone Boulevard E-Mail [email protected] Accessible online at: Providence, RI 02906 (USA) www.karger.com www.karger.com/pps Tel. +1 401 455 6457, Fax +1 401 455 6235, E-Mail [email protected] motor disturbance, psychiatric comorbidity, axis II per- an with PD who refused to take using cogni- sonality features and functional impairment [3, 7–9]. tive therapy. However, we were unable to identify any Compared with nonpsychotic depression, PD is charac- full-scale clinical trials of psychotherapy specifically for terized by a longer duration of illness, more frequent hos- PD. Cognitive behavior therapy (CBT) – a general term pitalizations and relapses and a greater likelihood of re- we use here to refer to the family of closely-related cogni- current psychotic symptoms [10–12] . Further, the poorer tive and behavioral interventions – has been found to be outcomes in PD have been shown to be independent of efficacious either alone or in combination with medica- initial symptom severity, and patients continue to show tions to treat severe forms of depression [20, 21] . Further, poorer outcomes even after acute psychotic symptoms emerging evidence suggests that CBT produces medium dissipate [12–14] . Research suggests that clinicians often effect size gains beyond ‘treatment as usual’ for patients fail to thoroughly assess for psychotic symptoms and pa- with primary psychotic disorders [22, 23]. Although tients tend to underreport symptoms due to or some past research has included small numbers of pa- embarrassment [15]. The number of differences between tients with PD [24] , the vast majority of psychotherapy psychotic and nonpsychotic subtypes has led some to ar- studies have excluded these patients from trials. gue that PD should be recognized as a unique diagnostic There also is a paucity of research investigating wheth- entity [14] . er the poorer outcomes found in patients with psychotic versus nonpsychotic depression apply to treatments that include pharmacotherapy and psychotherapy. Gaudiano Current Somatic Treatments for PD et al. [13] recently reported response to combined treat- ments in patients with PD. The data were pooled from Patients with PD show a poorer response to antide- clinical trials in which patients with psychotic and non- pressant treatment with tricyclic or selective serotonin psychotic major depression were provided with effica- reuptake inhibitor medications alone compared with cious combined therapies ( plus cognitive, be- nonpsychotic depressed individuals [5, 6]. Many authors havioral or family therapies). Although similar in sever- suggest that plus treatment ity during acute hospitalization, patients with PD showed is superior to treatment with either medication alone, al- greater depression severity at postoutpatient treatment though the results have not always been consistent. In a and at 6-month follow-up. Following treatment, patients recent Cochrane Systematic Review, Wijkstra et al. [16] with PD were over 4 times as likely to exhibit severe levels concluded that currently there are insufficient data to of and depression. The findings indi- support the superiority of combined antidepressant and cated that current state-of-the-art combined treatments antipsychotic treatment compared to antidepressant may have poorer efficacy in depressed patients with psy- monotherapy. Additional evidence suggests that electro- chotic symptoms, suggesting the need for adapted treat- convulsive therapy is an efficacious treatment for PD. ments better tailored to the needs of this population. Electroconvulsive therapy is at least as effective and in fact may be even more effective than combined antide- pressant plus antipsychotic therapy based on results from Pilot Findings Using an Acceptance-Based meta-analyses [5, 17] . However, electroconvulsive thera- Psychotherapy for PD py and neuroleptic medications have several disadvan- tages that can limit their effectiveness in clinical practice, Treatment Rationale and Description including side effects, safety concerns and symptom per- Feasibility data for the psychosocial treatment of PD sistence despite adequate treatment [5, 17, 18]. can be found in recent research using a brief form of Ac- ceptance and Commitment Therapy (ACT) [25] to treat acutely ill patients with psychotic spectrum disorders. Psychotherapy Response in PD ACT is similar to other emerging behavioral approaches that incorporate acceptance and elements, Given the limitations of current somatic treatments such as dialectical behavior therapy [26] . Preliminary ev- for PD, a clear role exists for psychosocial interventions idence from over 10 preliminary randomized trials sug- that can be used adjunctively to treat this disorder. In one gests the efficacy of ACT for treating a wide variety of of the only reports of its kind, Bishop et al. [19] described problems, including anxiety and substance use disorders a case study detailing the successful treatment of a wom- [27] . The results from 2 small trials comparing ACT to

272 Psychother Psychosom 2007;76:271–277 Gaudiano /Miller /Herbert

traditional CBT in depressed outpatients found that both Based on findings from an earlier trial [32], Gaudiano produced similar improvements in depression by post- and Herbert [33] tested the efficacy of ACT in a sample treatment, but that ACT resulted in earlier changes in the of hospitalized patients with psychotic symptoms, which believability of negative cognitions [27] . Whereas tradi- included PD, , and tional cognitive therapy [28] focuses on directly modify- . The patients were taught to increase ing dysfunctional thought content through rational de- their acceptance of unavoidable distress, to simply notice liberation and guided discovery, ACT focuses on modify- their psychotic symptoms without treating them as either ing the person’s relationship to his/her thinking more true or false, and to identify and work toward personally broadly. The goals of ACT are to promote increased ac- valued goals despite their symptoms [34] . In this pilot ceptance of unavoidable distress, to cultivate a mindful trial, 40 patients were randomly assigned to enhanced outlook (i.e. awareness of mental events as products of the treatment as usual (ETAU) or ETAU plus individual ACT rather than literal truths), to counteract excessive sessions, the number of which varied based on a ’s entanglement with cognitions and to work toward goals length of stay (average 3 sessions). At hospital discharge, that are consistent with patients’ personal values to mo- patients receiving ACT showed greater improvements in tivate change [25]. To achieve these aims, ACT employs a mood symptoms, -related distress and be- variety of strategies, including the use of metaphors and lievability, illness disability and clinically significant stories to communicate treatment concepts and behav- change. The groups did not differ in the frequency of psy- ioral exercises to increase a person’s willingness to con- chotic symptoms reported and both groups showed sig- tact the discomfort that often accompanies change ef- nificant decreases from before to after treatment. Al- forts. though the sample size was only modest, the ACT group ACT theorizes that is largely the re- had a 38% reduction in rehospitalization rates compared sult of experiential avoidance, which involves the overi- with ETAU alone by 4-month follow-up. dentification with and excessive negative evaluation of internal events (e.g. thoughts, emotions, memories), a Treatment Response in Patients with PD concomitant unwillingness to experience them, and the As a significant proportion of the sample in the ACT resulting efforts made to control or escape from them for psychosis study was diagnosed as having PD (ETAU that can interfere with functioning and lead to behavior + ACT: n = 9, ETAU only: n = 9), we conducted secondary inflexibility [27, 29]. From a clinical perspective, patients analyses to investigate whether these patients also bene- high in experiential avoidance tend to engage in multiple fited from psychotherapy provided during hospitaliza- maladaptive strategies in attempts to remove internal tion. The subsample of patients diagnosed as having PD sources of distress, which often lead to increasing social based on admission diagnosis was 56% female and 78% isolation, obsessive rumination, suicidality and thought unmarried. The average age was 40 years old (SD = 12). disturbance. Studies using clinical and nonclinical sam- All participants were African-American (n = 17) or His- ples demonstrate that experiential avoidance is strongly panic (n = 1). In addition, 22% were homeless and 56% correlated with various forms of psychopathology, in- were receiving disability compensation. The average cluding depression [29] . Research also suggests that length of hospital stay was 9 days (SD = 8) and the pa- chronic experiential avoidance may produce a paradoxi- tients received an average of 3 ACT sessions. Most gradu- cal effect, in that attempts to escape or control unwanted ated high school or had an equivalency diploma (61%). private events may actually increase their frequency or Descriptive statistics for outcome measures are re- intensity in the long run [30] . The negative effect of avoid- ported in table 1. Because of the small sample size, we ance-based coping also has been implicated in psychosis. limited our analyses to clinically meaningful outcomes For example, Tait et al. [31] found that a ‘sealing-over’ re- using nonparametric tests. The results indicated that covery style after acute psychosis predicted several nega- 44% of the PD patients in the ACT group showed clini- tive outcomes independent of into illness. ‘Sealing cally significant improvement by discharge ( 62 SD over’ is defined as a coping method in which the patients change from before to after treatment) on Brief Psychiat- minimize the significance of their psychotic symptoms ric Rating Scale (BPRS) [35] total scores compared with and are disinterested in exploring aspects of the experi- 0% of the ETAU only group, 2 = 5.14, p ! 0.05. The rates ence in treatment, which has been shown to predict in- of clinically significant change on BPRS mood symptoms creased depression and impaired psychosocial function- subscale were 70% in the ACT group compared with 30% ing independent of the person’s insight into illness. in the ETAU only group, 2 = 3.60, p = 0.058. No signifi-

Treatment of Psychotic Depression Psychother Psychosom 2007;76:271–277 273 Table 1. Baseline and discharge scores for patients with PD treated in an inpatient hospital setting

ETAU (n = 9) ETAU + ACT (n = 9) baseline discharge 62 SD baseline discharge 62 SD

BPRS (18-item) Mood symptom subscale 25.181.9 18.784.9 3 (33) 27.082.1 18.084.2 7 (77) Psychotic symptom subscale 10.082.5 8.482.3 0 (0) 9.983.7 7.282.3 1 (11) Total 55.485.0 43.386.6 0 (0) 58.087.3 42.688.0 4 (44) Self-ratings of hallucinations Frequency 5.181.6 3.881.8 6.081.5 4.781.9 Distress 6.382.9 7.381.7 9.181.7 6.783.3 Believability 8.381.7 7.682.5 8.682.6 5.984.2

Values are means 8 SD. Figures in parentheses represent the percentage of patients. Clinically significant improvement defined as 62 SD change ().

cant differences were found between the rates of clini- Considerations in the Psychological Treatment of PD cally significant change on BPRS positive symptoms sub- scale (p = n.s.). Given their documented and robust success in treating The patients were asked to rate the frequency (1 = none mood and psychotic disorders, CBT-based interventions to 7 = almost constant), believability (0 = none to 10 = appear promising for treating PD. However, we recom- total belief) and distress (0 = none to 10 = very severe) mend caution in inferring that treatments that work well associated with their hallucinations using single-item with nonpsychotic depression will be equally effective Likert ratings. Mann-Whitney U tests were computed on with PD. As noted, our data suggest that patients with PD change scores of hallucination ratings. Pre- to posttreat- respond less well to traditional psychotherapy than those ment improvement in hallucination-related distress was with nonpsychotic depression and thus may require spe- significantly greater in the ACT group (mean = –2.4, cific adaptations for optimal results [13] . Therefore, the SD = 3.3) compared with the ETAU group (mean = 1.0, following suggestions should be viewed as tentative and SD = 2.2), which worsened slightly, z = 1.97, p ! 0.05. are subject to change based on much needed empirical Three patients from each condition were rehospitalized verification. Although other forms of therapy may also over 4-month follow-up. prove efficacious (e.g. family therapy), we limit the cur- It is important to note that the pilot trial was not with- rent discussion to CBT approaches. out limitations. First, treatment was delivered in a brief format exclusively while patients were hospitalized. Pa- How Should Therapy Be Adapted? tients with severe conditions such as PD are likely to ben- Although a variety of common CBT techniques (e.g. efit from continued treatment and follow-up after dis- cognitive restructuring, behavioral activation, problem charge. Second, although the results obtained from symp- solving, anxiety management techniques) may prove use- tom measures were promising, assessors and hospital ful for treating PD, adaptations may be necessary. For ex- staff were not blind to treatment allocation. Third, the ample, the therapist should proceed cautiously and ten- number of patients with PD in the sample was relatively tatively with the cognitive restructuring element of tradi- small and diagnoses were not based on structured clini- tional cognitive therapy when treating psychotic in cal interviews. Finally, although rehospitalization rates contrast to nonpsychotic depression. Pursuing disputa- were assessed 4 months after discharge, the longer-term tion strategies too early or vigorously can alienate the pa- effects of the intervention on symptoms and functioning tient and cause premature termination [36] . One poten- were not assessed. It will be important for future research tial advantage of acceptance-based models of CBT such to evaluate the efficacy of ACT in larger samples of pa- as ACT is that they focus more on increasing acceptance tients with PD using more stringent methodology. of internal distress than altering putatively dysfunctional

274 Psychother Psychosom 2007;76:271–277 Gaudiano /Miller /Herbert

thinking patterns to promote behavior change. The two chotic medication is withdrawn, psychotherapy can be pilot studies of ACT for psychotic inpatients suggest that instated to help patients monitor residual symptoms and acceptance techniques targeting psychotic symptoms can to learn to cope more effectively with stressors to prevent be used with the majority of patients in the first session symptom reoccurrence. Moreover, sequential treatment [32, 33] . However, when employed during less acute peri- with mindfulness-based CBT has been shown to reduce ods of illness, traditional cognitive restructuring tech- relapse rates in those at high risk (i.e. with multiple past niques may help the patient to develop skills in identify- depressive episodes) [38] and therefore may prove useful ing and countering residual symptoms of psychosis to for those with PD, given the recurrent nature of the dis- prevent more severe relapses [36] . In addition, it is impor- order. tant to consider potential cognitive deficits and limita- tions, which frequently are problems in PD [5] . The ther- What Level of Therapist Skill Is Necessary? apist can help mitigate this issue by focusing more on An additional consideration is the level of therapist concrete behavioral goals and strategies when dealing skill necessary for treating patients with PD. Although with severely ill patients. The therapist can further tailor many therapists may feel quite comfortable treating de- treatments for patients with cognitive limitations by ex- pression, they may lack experience treating severely ill plaining treatment concepts using simpler language (e.g. populations, including those experiencing psychosis. use of metaphors and stories in ACT), reviewing session Some researchers are beginning to address this issue. A information frequently and providing visual aids and pa- recent study demonstrated that CBT for psychosis could tient handouts/workbooks. be effectively provided by psychiatric nurses receiving minimal training [39] . Seminars and workshops on CBT Should Therapy Be Delivered Sequentially or for severely ill populations are frequently offered at pro- Concurrently? fessional conferences such as the annual meeting of the Some may argue that patients hospitalized with PD Association for Behavioral and Cognitive Therapies. We will be too severely ill to benefit from ‘talk’ therapy. How- recommend that a therapist with experience treating pa- ever, available research indicates that acutely ill patients tients using CBT for depression seek out additional train- with severe mood and psychotic disorders can in fact ing first and then obtain supervision from an experi- benefit from adjunctive psychosocial interventions [21, enced professional familiar with these issues for initial 22] . During our research, we found it appropriate to be- cases. gin therapy with most hospitalized patients when they were able to participate in other group therapy on the unit What Potential Problems Should Be Anticipated? after initial psychiatric stabilization with medications. It Patients with PD are 2–5 times more likely to have a is important to emphasize that psychiatric stabilization history of suicide attempts [2] . Ongoing assessment and also is required for informed consent. Also, psychother- monitoring of suicidality constitutes an important com- apy should be provided only after consultation with the ponent of treatment. Further, the therapist and patient patient’s treating medical team. Regarding the treatment should collaborate to develop a mutually agreed upon of outpatients, review of the literature suggests that con- safety plan detailing actions to be taken in response to current pharmacotherapy and psychotherapy is appro- increased suicidal ideation. In addition, nonadherence to priate for most patients [21] , again assuming close con- medication and other treatments is a frequent problem in sultation with the treating . Further, it is im- PD [15] . The therapist should routinely monitor the pa- portant for the therapist to provide a therapeutic rationale tient’s level of adherence to pharmacotherapy and psy- that does not undermine the other somatic treatments chotherapy. The therapist can help the patient problem that the patient may be receiving. For patients with severe solve issues surrounding medication management and mental illnesses, a diathesis- model of illness can be promote closer consultation with the treating psychia- used to acknowledge the role of genetic and neurobio- trist. Also, the involvement of a significant other to im- logical factors, yet account for environmental influences prove treatment adherence is a commonly used strategy (e.g. stressors, learning history) and other psychological in behavioral interventions. We have found it useful to processes (e.g. experiential avoidance) affecting the pa- hold 1 or 2 joint sessions with significant others (e.g. tient’s course of illness [36]. spouse, parent, sibling) to discuss ways in which the fam- A sequential approach also could be considered [37] . ily can support the patient’s treatment goals. After acute psychotic symptoms dissipate and antipsy-

Treatment of Psychotic Depression Psychother Psychosom 2007;76:271–277 275 Are There Any Contraindications? acutely ill samples, study designs that focus on the re- We found the ACT intervention to be generally well cruitment of patients initially hospitalized may aid in en- tolerated by patients and supported by hospital staff. rollment efforts. However, ethical issues become even However, we recommend caution when using formal, in- more salient when dealing with hospitalized patients, tensive meditation techniques with acutely ill psychotic and protocol safeguards are necessary to ensure informed patients, as some case reports suggest that intensive med- consent. Structured clinical interviews administered by itation may exacerbate psychosis [40] . ACT employs a trained diagnosticians should be used to assess patients number of nonmeditation-based exercises that foster for study inclusion, as PD is often difficult to differen- mindfulness using alternative techniques [34] . Further, tially diagnose. In addition, recent research suggests that patients with PD may experience periods of acute illness the BPRS is a psychometrically sound instrument that that can make it difficult to proceed with the therapy. has good sensitivity and specificity for assessing PD [41] . Therapy can be suspended until the patient is stabilized. Finally, it will be important for studies to employ a range During these periods, the therapist can collaborate with of outcome measures (e.g. symptom severity, psychoso- other providers to assess and monitor the patient to de- cial functioning, treatment adherence, long-term out- termine the need for hospitalization. Finally, we recom- comes) that assess clinically (in addition to statistically) mend tailoring therapy to patient severity so as not to significant improvement in order to determine the poten- overwhelm the individual with treatment goals and strat- tial benefits of psychotherapy for PD. egies. For example, the typical 1-hour session may be di- vided into 2 half-hour sessions during hospitalization or periods of acute illness. Conclusion

Adjunctive, psychosocial treatments for patients with Considerations for Future Research PD are urgently needed due to the increased risk of mor- bidity and mortality associated with this population. Un- As the previous review highlights, there is an urgent fortunately, treatment development in this area currently need to conduct systematic research on the psychosocial is lacking, as patients with psychotic features have been treatment of PD. We believe that CBT-based interven- excluded historically from psychotherapy trials of depres- tions, including newer acceptance-based approaches, are sion. Our pilot data suggest that patients with PD can ben- good candidates for further testing. As pharmacotherapy efit from modified CBT approaches. However, further re- is considered the first-line treatment for PD, studies search is needed to develop comprehensive adjunctive ap- should first examine whether combined pharmacothera- proaches for treating patients during all phases of illness. py and psychotherapy result in better outcomes than pharmacotherapy alone. If this can be confirmed, further A c k n o w l e d g m e n t research should be conducted to examine the possible mechanisms of action of effective psychological treat- We would like to thank the anonymous reviewers for their ments for PD. As PD is likely to be most prevalent in helpful feedback on an earlier draft of the manuscript.

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