Combining Cognitive Therapy and Pharmacotherapy

Journal of Cognitive Psychotherapy: An International Quarterly Volume 21, Number 1 • 2007

Combining Cognitive Therapy and Pharmacotherapy for Schizophrenia David Kingdon, MD, MRCPsych University of Southampton, UK

Shanaya Rathod, MD, MRCPsych Hampshire Partnership Trust, Southampton, UK

Lars Hansen, MRCPsych Farook Naeem, MRCPsych University of Southampton, UK

Jesse H. Wright, MD, PhD University of Louisville, Kentucky

Cognitive therapy (CT) is now recognized as an effective intervention for schizophrenia in clinical guidelines developed in the United States (APA, 2006; Lehman et al., 2004) and Europe (e.g.. National Institute of Clinical Excellence, 2002). However, empirical studies of CT for schizophrenia, cited as the evidence base for these recommendations, have been conducted solely with patients treated with concurrent medication. It has been a priority in some studies to enhance collaboration with the use of medication and insight into the illness for the individual patient (Kemp, Hayward, Applewhaite, Everitt, & David, 1996); and in most studies, such collaboration has been an integral part of the CT intervention. This article discusses potential interactions between medication and therapy, briefly outlines commonly used medication regimens for schizophrenia, details possible methods to improve adherence to pharmacotherapy, and explores issues encountered in collaboration in combined pharmacotherapy and CT. Finally, we discuss strategies for managing situations in which clients do not want to take medication. Keywords: pharmacotherapy; cognitive theraphy; schizophrenia; psychosis

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edication may enhance CT through direct effects on symptoms, for example, improvement with regard to agitation, concentration, distractibility, or iUogical thinking. There also can be indirect effects, such as reducing suspicion of the therapist's intentions. Another possible favorable influence is a heightened expectation of a good response to treatment. Some patients who are prescribed medication, especially if they have played a role in choosing the regimen and believe it may help, can experience an increase in hopefulness and a more positive attitude about engaging in CT.

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© 2007 Springer Publishing Company

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Cognitive therapy may also have a positive influence on pharmacotherapy. In studies of depression and obsessive-compulsive disorder (OCD), evidence is emerging that CT may be a "biological treatment" that works in concert with medication on reversing neurobiological defects (Wright, 2004). Although there have been no studies of this type in patients with psychoses, research in this area would be of great interest. One possible effect of CT on pharmacotherapy of schizophrenia that has been investigated is its impact on adherence. We will detail methods of improving adherence to pharmacotherapy later in this article. Medication, however, has the potential for detracting from CT in some situations. For example, side effects may be interpreted in a delusional manner. Also, the prescription of medications can have a negative influence on the therapeutic relationship. Patients may assume that doctors push medications because they don't want to talk or don't have time for patients. Also, there may be negative beliefs or memories about medication that color the therapeutic relationship (e.g., "My hallucinations got worse on risperidone. The doctor didn't believe me, and he prescribed the same medication. He must want to hurt me"). Delusional elaboration of side effects is a common occurrence, especially where potential reactions have not been explained prior to commencing the medication. For example, impaired sexual libido and performance may be interpreted as a change in gender from a man to a woman; dystonic reactions may be interpreted as effects of control by external forces; or tremor may be interpreted as electric currents flowing through the body. One of the more frequently encountered delusional beliefs is that the person is being poisoned by medication. Also, patients may become convinced that caregivers and others have been giving medication to them surreptitiously, especially in food. Occasionally such beliefs may be correct, when caregivers are desperate to maintain adherence to medication. While most, if not all, patients who are acutely psychotic and severely agitated will require medication, the timing of the introduction of cognitive therapy needs careful consideration. Similarly, consideration needs to be given to the methods to use early in treatment, in the middle phase of treatment with chronic patients, and in maintenance therapy when CT is minimized and the patient is seeing a clinician primarily for medication management. MEDICATION FOR SCHIZOPHRENIA The first compound that was shown to be effective in the treatment of schizophrenia and other psychotic disorders was chlorpromazine, an antihistaminic drug incidentally observed to possess antipsychotic effects. The discovery of the mechanism of action of antipsychotics dates back to the 1960s, when researchers found that these compounds act as dopamine receptor antagonists. The "typical" antipsychotic drugs were nonselective in their blockage of dopamine (D2) receptors. Therefore, they not only acted on the mesolimbic dopaminergic pathways (which mediate their therapeutic effects for positive symptoms) but also affected the striatal regions in the basal ganglia, and resulted in the appearance of extrapyramidal ("parkinsonian") side effects, for example, rigidity, dystonia, tremor, akathisia ("restlessness syndrome"), and longer term involuntary movements (tardive dyskinesia). Typical or classical antipsychotics are usually grouped by chemical structure: phenothiazines (for example, chlorpromazine), butyrophenones (for example, haloperidol), thioxanthenes (for example, flupenthixol), benzamides, and so on. Clozapine, discovered in the early 1970s, possesses antipsychotic activity while having a very low risk of inducing extrapyramidal side effects. For this reason, it was defined as an "atypical" antipsychotic drug. Later, other beneficial properties, such as improvement of negative symptoms and cognitive dysfunction, and efflcacy in neuroleptic-resistant schizophrenia, were included in the definition of "atypical" antipsychotics (Serretti, De Ronchi, Lorenzi, & Berardi, 2004). Unfortunately, clozapine has another set of side effects, such as a lowering of the white blood cell

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Combining Therapy for Schizophrenia

count, weight gain, sedation, and seizures, which have limited its use. Nevertheless, clozapine is widely recognized as an especially effective antipsychotic medication and may be used when safer drugs fail to relieve the symptoms of schizophrenia. Several atypical antipsychotics, which have become available for the treatment of schizophrenia, are at least as effective as conventional treatment, have far fewer extrapyramidal side effects, and do not have the white blood cell effects of clozapine (Geddes, Freemantle, Harrison, & Bebbington, 2000). Their presumed mechanisms of therapeutic action vary and are no longer limited to dopamine (D2) receptor antagonism. For example, risperidone and quetiapine are mixed serotonin (5HT2-A) and dopamine receptor antagonists. Amisulpride is a pure D2/D3 (dopamine) antagonist and clozapine, zisprasadone, and olanzapine are pluripotent receptor antagonists (Cookson, Taylor, & Katona, 2002), which work at various receptor sites. Atypical antipsychotics may in some cases raise serum lipid and/or glucose levels. Numerous novel drugs now in development have a variety of receptor affmities and other supposed therapeutic effects (Mortimer, 2004).

COGNITIVE THERAPY AND ADHERENCE TO PHARMACOTHERAPY Terminology in this area has been controversial. A frequently used term, compliance, suggests a treatment approach defined by the prescriber, usually a physician, to be followed by the patient. Adherence has a similar meaning but suggest the possibility of negotiation over the treatment regimen. The word concordance suggests more agreement about what is to be prescribed. Some experts strongly recommend that the term compliance be avoided, while others use the descriptors interchangeably. An approach using cognitive therapy inevitably involves collaboration and an exploration of the client's beliefs about his or her problems and the possible ways of understanding and coping with them, including the use of medication. Thus, we typically use the word adherence to describe medication-taking behaviors in patients treated with CT. Nonadherence to antipsychotic medications in schizophrenia has a significant impact on the rate of relapse, prognosis, and resource utilization in persons with schizophrenia (Buchanan, 1996; Green, 1998; Hayward, Chan, Kemp, Youle, & David, 1995; Vaughn & Leff, 1976), resulting in high costs for the services and society. The incidence of nonadherence in psychosis has been reported to be between 10% and 80% (Babiker, 1986; Renton, Affleck, Carstairs, & Forrest, 1963; Van Putten, 1974; Young, Zonana, & Shepler, 1986). However, it is difficult to obtain an accurate estimate of rate-of-adherence problems because of different ways of defining and recording failure to take medication as prescribed. Relying on patient reports, caregiver feedback, or pill counts can lead to erroneous conclusions about the rate of pill-taking behavior. Nevertheless, experienced clinicians are well aware of the magnitude and significance of nonadherence in schizophrenia. Poor adherence can be due to drug-related factors (e.g., complexity of prescription, side effects, or cost), patient-related variables (e.g., illness symptoms, comorbidity, insight, decision-making capacity, belief system, family infiuences, or sociocultural environment), and physician-related factors (e.g., communication or psychoeducational style) (Carvajal, 2004). Systematic reviews and a meta-analysis of various approaches to enhance adherence to medications in schizophrenia have yielded inconsistent results, refiecting the many shortcomings of the studies included in the review and meta-analysis. Most of the interventions tend to be rather complex and resource-intensive. One of the consistent findings has been the limited impact of approaches based on psychoeducation alone, without additional behavioral, family, and economic support. Not only does the content of any adherence intervention approach seem to be important, but the timing of it is also relevant—during acute phases or, particularly, when stabilized (Awad, 2004).

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Persons with schizophrenia often deny or are unaware of their mental illness (Amador et al., 1994). Illness symptoms may be attributed to life stresses, outside forces, or other predicaments, and thus the need for medication may not be recognized. Attitudes and belief systems related to illness, specifically mental illness, contribute toward help-seeking behavior (Sullivan, Burnam, Koegel, & HoUenberg,, 2000) and the degree to which persons follow treatment recommendations (Amador et al,, 1993). Family input can undermine the treatment plan or provide strong support for taking medication. Social and cultural influences can also play an important role. Patients are more likely to deny mental illness if they come from a social group in which it is highly stigmatized. Studies have suggested that clients' attitudes and degree of knowledge about mental illnesses tend to resemble those of the people in their background rather than those of mental health professionals (Bentinck, 1967). There is substantial diversity in the representation of mental illness that members of different social groups bring to their transactions with their doctors (Johnson & Orrell, 1995). Although awareness of illness is important, recognition and acceptance of a diagnosis can occasionally lead to the development of depression in psychotic clients (Birchwood & Iqbal, 1998) and suicidal ideation (Amador et al., 1996). Therefore, any intervention targeting these issues requires a sensitive and collaborative approach. Two general methods have been used in cognitive therapy to promote collaboration with pharmacotherapy regimens: the direct route—specific discussion of medication and associated beliefs, in addition to psychoeducation and cognitive and behavioral interventions; and a more gradual approach aimed at working with individuals to assist them to better understand their problems, learn to cope with these difficulties, and see how medication might assist with this process. Both approaches have their place. However, where medication is being actively resisted, the latter strategy is typically used initially. Before directly addressing adherence, the focus is on developing a cooperative therapeutic relationship, completing a full assessment and formulation, and eventually discussing the use of medication as a component of the overall treatment effort. As part of this broader approach, cognitive therapy involves working toward the patient's considering the possibility that hallucinations that appear to originate externally may be internal phenomena ("from your own mind"); and that delusional beliefs, for example, that others are interfering with your life, are persecuting you, or making comments about you, may be better explained as perceptual distortions. If this shift in understanding the phenomena of hallucinations and delusions occurs, patients may be more likely to recognize the potential benefit of medication in reducing such distressing experiences and in improving coping capacity. When patients believe their neighbors are talking to them through the walls of their house, it may seem illogical to take medication to prevent it. However if they can entertain the possibility that they might be mistaken, the prospect of help from medication may be more reasonable. A diagnosis of mental illness, specifically schizophrenia, will usually have been discussed. Reactions to learning this diagnosis can be positive but more often are negative. When clients give a positive response, they may have been relieved to have been given a name for their problems and a medical diagnosis that legitimizes their experiences. Rather than seeing themselves (and possibly being designated by others) as "idle" and "useless," they are able to reconceptualize themselves as persons suffering from an illness. When these modifications in self-concept occur, there can be added benefits: reduced guilt, increased understanding and acceptance, and improved ability to deal with the practical issues (e.g., financial concerns, housing, and social support) associated with schizophrenia. If such acceptance occurs, adherence to medication regimens is usually enhanced, although issues of effectiveness and side effects may remain. When negative or neutral responses are given to discussions about diagnosis, corresponding difficulties with medication usually arise. In a recent study (Kingdon et al., in press), such responses were given by 92% ofthe sample. Some of these are related to the use of terminology, as other evidence (Rathod, Kingdon, & Turkington, 2003)

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suggests that acceptance of treatment is far more important than acceptance of "illness" in the improvement in symptoms of schizophrenia. It may therefore be constructive to develop terms for illness that can be shared and understood by both patient and clinician. For example, some patients find the descriptors "nervous breakdown" or "mental health problems" much more acceptable than "mental illness" or "schizophrenia." We have also been developing alternative terms for subgroups of schizophrenia (drug-related, sensitivity, traumatic, and anxiety psychoses: Kingdon & Turkington, 2005) that have seemed plausible and meaningful to clients. Caregivers and friends can be supportive but may also have concerns of their own about terminology and medication usage. It may be that caregivers and friends have been influenced by previous negative experiences with mental health services or medication. Such negative experiences, or denial that the patient is ill, may lead them to influence the person against the use of medication and cooperation with services. Patients may not wish to go against their caregivers' advice, even when they themselves accept that medication is necessary. Where agreeable to patients, direct work with caregivers or friends may help promote understanding and enlist their support in providing needed treatment. Psychoeducation about schizophrenia and available treatments is a key element of the cognitive therapy approach to this disorder. Ideally, the educational process will be highly collaborative instead of didactic or forced. We have seen many patients in consultation who have been "told" over and over again about the nature of their condition, but still do not believe that they have an illness or could benefit from treatment. The collaborative approach involves relationship building and an assessment of what the patient knows, wants to know, and is ready to know. For the best effects, educational methods should be individualized and geared to each patient's needs and capacities. Information about medication usually includes how it works (as far as we know), significant side effects (including how side effects can be managed), and sometimes the evidence for its effectiveness. We typically provide this type of education through discussions in therapy sessions. Drug information sheets can be employed, but sometimes these resources may be confusing or may overload people with too much detail, especially if a patient is acutely psychotic, is quite paranoid, or is having significant problems with concentration. When an agreement has been reached that medication will be used, negotiation regarding the choice of drug(s) and doses can help promote future adherence. Although patients usually respect the judgment ofthe prescriber, they may wish to express preferences, considering their previous experiences with medications, things they have learned about drug therapy, or potential side effects. For example, one of our patients who uses the Internet regularly has come to treatment sessions with printouts that describe new medications she wants to try. Sometimes the negotiation process may require the prescriber to defer using his or her preferred option in favor of another safe and clinically indicated approach that can be endorsed fully by the patient. Generally, the likelihood of adherence to the pharmacotherapy regimen will be higher when the patient finds it understandable, reasonable, clear, and acceptable. In situations where the therapist is not the prescriber, it can also be very helpful to discuss previous history with medication, current preferences, and concerns. Nonmedical therapists can assist patients in clarifying their thoughts about medication and in establishing a negotiation process with the pharmacotherapist, either through role-playing the discussion with the potential prescriber or by more direct advocacy. Negotiation is not always successful in reaching agreed goals in medication management. When this problem occurs, the reasons should be made explicit (e.g., a wish to remain autonomous or avoid specific side effects such as potential weight gain). In most instances, there can be an "agreement to differ," along with continuing therapy sessions to discuss pharmacotherapy and other matters.

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Despite the potential problems noted above, the cognitive therapy approach typically facilitates good therapeutic relationships and willingness for patients to utilize specific cognitive and behavioral interventions to improve adherence. Cognitive methods can include eliciting and modifying automatic thoughts and core beliefs about medication. One of the approaches that we commonly use is to target a maladaptive belief with an "examining the evidence" exercise. The treatment of an inpatient with schizophrenia who was hesitant to take an atypical antipsychotic medication illustrates this type of intervention. This man had become convinced that the medication was "experimental," despite frequent reassurances from the nursing staff. The evidence that he listed for this conclusion included the following: (1) side effects had been experienced with many other medications; (2) his belief that doctors may tell him only part ofthe story about medication; (3) his distrust of previous psychiatrists; and (4) the fact that doctors were recruiting for a research study in the clinic that he attended. At first, he could think of little evidence against the belief that the medication was "experimental," but in collaborative questioning was able to note that (1) the medication had been approved by a governmental agency (the Food and Drug Administration; FDA) for use; (2) he did trust the current therapist enough to consider that the medication was not experimental and he was not being tricked into taking it; and (3) consent forms were required for any experimental drugs. As is often the case, the exploration of "evidence for" maladaptive beliefs can have significant benefits. Listing the reasons why this patient thought that the drug was experimental led to a profitable discussion about side effects, his experiences with previous treatment, and his trust in physicians and other health care professionals. The end result of this therapeutic work was a decision by the patient to give the medication a try and to fully report any of his concerns or possible side effects to the prescribing physician and therapist. He agreed that it would be helpful to build trust by openly discussing his questions about taking the medication. Behavioral methods can also have a positive effect on medication adherence in patients with schizophrenia. Some of the commonly used methods are reminder systems, such as 7-day pill containers, pairing pill taking with a daily activity (e.g., getting ready for bed, brushing teeth, mealtime) if the patient reliably follows a routine, behavioral contracting, and developing strategies for overcoming barriers to adherence (e.g., running out of medication, missing appointments with a doctor, experiencing a side effect) (Wright, 2004). With persons who have high risk for nonadherence and subsequent relapse, it may be helpful to write out a detailed plan containing elements that both patient and therapist agree may help promote the reliable use of medication. USE OF COGNITIVE THERAPY IN THE ABSENCE OF MEDICATION Cognitive therapists have not produced direct evidence of cognitive therapy for psychotic patients who do not accept medication. It has been a priority to develop cognitive therapy in conjunction with medication use. However, despite developing a collaborative relationship and providing appropriate psychoeducation, some patients decide not to take medication. In these circumstances, continuing therapy may be acceptable to them and assist them in maintaining contact with services. With time, they may return to discussions about medication and become prepared to try it again (see Illustrative Case Study).

ILLUSTRATIVE CASE STUDY Frank is now 51 but had his first psychotic episode in his early 20s after a weekend in which he consumed various substances, including amphetamines, LSD, and cannabis. Subsequently he had a number of admissions to hospitals. But, over the past 10 years he

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has been maintained in the community. He continues to hear abusive voices and to receive messages from the television which take the form of announcers criticizing him or referring nonsensically to him. He lives alone but has a few friends. His prescribed medication usage has been erratic. Cognitive therapy, with assistance from care managers, has been used as part of the approach to his psychiatric management. He has not been convinced that medication helps him but he agreed for a period to take an atypical antipsychotic, risperidone. It is unclear how good his adherence was to the regimen that had been established. Work in cognitive therapy on his voices and delusions of reference helped him understand that they were hallucinations and inaccurate beliefs. He attributed them to his initial drug experiences and a continuing "drug-related" psychosis. However, he did not accept that he had schizophrenia. Frank decided that the medication was not helping him, that he was experiencing side effects, and he announced that he was going to stop it. His therapist/prescriber was concerned that this action might put him at risk of relapse and increasing symptom severity but agreed that the medication had not eliminated his symptoms. A plan was negotiated wherein gradual reduction of medication would occur. The side effects Frank described were tremors and sedation. Treatment of the tremor using anti-parkinsonian medication had been only partially effective. The medication was reduced over a period of several months, and eventually Frank asked to stop it altogether. Initially there was no worsening of his condition, but then his sister contacted the mental health service to report concerns that he was increasingly neglecting himself. However it turned out that, while he had some increase in the intensity of his voices, he was also experiencing stress due to the fact that his state financial benefits had been cut seriously. He did not wish to recommence medication. Instead, he focused on representations to the benefits office to reinstate his lost benefits. After a few months of continuing problems, he again discussed the possibility of medication, because the voices were continuing to cause him distress. In collaboration with him, newer medication was prescribed with fewer side effects, and he has recommenced it. DISCUSSION Schizophrenia is a major cause of distress and disability. Medication has reduced symptoms in a substantial proportion of patients, but many remain resistant to its effects or fail to adhere to treatment regimens. Psychoeducation can help in providing greater understanding of the evidence for the use of medication and the ways in which it can help. But, when patients do not believe that they are ill—specifically that they have schizophrenia—or require treatment, such education may not seem relevant or be accepted. Cognitive therapy takes a broader view of the problems experienced by clients, so that the very nature of the experiences is examined. Specific discussion of whether or not the individual wishes to take medication will occur and the reasons for and against will be weighed up. Explanations of the individual experiences will be developed from a formulation so that it is possible, for example, to understand that hallucinations may be arising from the mind, rather than the CIA (or other explanation). With such reattribution, medication can become more relevant and acceptable. Specific interventions such as those described can also assist in enhancing adherence. Where clients refuse to take medication, it is possible to continue worldng with them using a cognitive therapy approach. Collusion with the patient in nonadherence is avoided by frank discussion of the alternatives and their possible consequences. Allowing the patient to take part in the decision-making process can be seen as empowering. Clients may at a later stage return to using medication, as in the case described above. It is possible that some patients may

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benefit from therapeutic support in the absence of medication. However, no empirical evidence has been provided to support the use of cognitive therapy alone as a treatment alternative to pharmacotherapy.

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Kingdon, D. G., & Turkington, D. (1994). Cognitive-behavioral therapy of schizophrenia. New York: Guilford. Kingdon, D. G., & Turkington, D. (2002). A casebook guide to cognitive behaviour therapy; Practice, training and implementation. Chichester, UK: Wiley. Kingdon, D. G., & Turkington, D. (2005). Cognitive therapy of schizophrenia. Guide to individualized evidence-based treatment. Series Editor: J. Persons. New York: Guilford. Lehman, A. F, Kreyenbuhl, J., Buchanan, R. W, Dickerson, F. B., Dixon, L. B., Goldberg, R., et al. (2004.) The schizophrenia Patient Outcomes Research Team (PORT): Updated treatment recommendations 2003. Schizophrenia Bulletin, 30(2), 193-217. Mortimer, A. M. (2004). Novel antipsychotics in schizophrenia. Expert Opinion on Investigational Drugs, 13(4), 315-329. National Institute for Clinical Excellence. (2002). Clinical Guideline 1; Schizophrenia. Retrieved November 14, 2003, from www.nice.org.uk Rathod, S., Kingdon, D., & Turkington, D. (2003). Insight and schizophrenia. Paper presented at the Psychological Interventions in Schizophrenia Conference, Oxford, UK. Renton, C, Affleck, J., Carstairs, G., & Forrest, A. (1963). A follow up of schizophrenic clients in Edinburgh. Acta Psychiatrica Scandinavica, 39, 548-581. Sensky, T, Turkington, D., Kingdon, D., Scott, J., Siddle, R., O'Carroll, M., et al. (2000) A randomized controlled trial of cognitive behavioural therapy for persistent symptoms in schizophrenia resistant to medication. Archives of General Psychiatry, 57, 165-172. Serretti, A., De Ronchi, D., Lorenzi, C, & Berardi, D. (2004). New antipsychotics and schizophrenia: A review on efficacy and side effects. Current Medicinal Chemistry, 11(3), 343-358. Sullivan, G., Burnam, M., Koegel, P, & Hollenberg, J. (2000). Ouality of life of the homeless mentally ill: Results from the course of homelessness study. Psychiatric Services, 51, 1135-1141. Van Putten, T. (1974). WTiy do schizophrenic clients refuse to take their drugs? Archives of General Psychiatry, 31, 67-72. Vaughn, C, & Leff, J. P. (1976). The influence of family and social factors on the course of psychiatric illness. British Journal of Psychiatry, 129, 125-137. Wright, J. H. (2004). Integrating cognitive-behavioral therapy and pharmacotherapy. In R. Leahy (Ed.), Contemporary cognitive therapy; Theory, research, and practice. New York: Guilford Press. Young, J., Zonana, H., & Shepler, L. (1986). Medication non-compliance in schizophrenia: Codification and update. Bulletin of American Academy of Psychiatry and Law, 14, 105-122. Correspondence regarding this article should be directed to David Kingdon, MD, MRCPsych, University of Southampton, Royal South Hants Hospital, Southampton, SO14 OYG, UK. E-mail; [email protected]