Mind the gap: bringing together psychopharmacology and cognitive behavioural therapy

Mental health interventions are often compartmentalised into psychological and pharmacological approaches, and there has been much debate as to which is superior. Methodological differences make their efficacy difficult to compare, and as both can be useful alone we should also explore their synergistic effects (Huhn et al., 2014). Current treatments could be improved considerably by encouraging collaboration across these disciplines in a united approach to mental health science (Holmes, Craske, & Graybiel, 2014). This was the aim of an event linking the British Association for Psychopharmacology (BAP) and the British Association for Behavioural and Cognitive Psychotherapies (BABCP) for the first time in their 40-plus year history. Marcus Munafò and Simon Blackwell chaired a symposium twice at each organisation’s annual conference in July 2015, with support from the charity MQ: Transforming Mental Health.

Catherine Harmer’s presentation demonstrated how experimental psychology could help us move beyond a neurochemical explanation of drug efficacy. Robust changes in emotional bias (e.g. face recognition, vigilance for threat) are evident after a single dose of antidepressant (Harmer et al., 2009) or Cognitive Behavioural Therapy (CBT) (Reinecke, Waldenmaier, Cooper, & Harmer, 2013). Crucially, these early changes predict the magnitude of therapeutic benefit at follow up. Additionally, this account of antidepressant action can explain why efficacy depends upon environmental factors such as social support (Shiroma, Thuras, Johns, & Lim, 2014). Thus, antidepressant drugs and CBT can act via common psychological mechanisms, which may help us identify new treatments, moderators of clinical efficacy, and responding subgroups.

Turning to addiction, Matt Field argued that inhibitory control can be seen as a core psychological dysfunction. Deficits on tasks requiring inhibition of a behavioural response, such as the Stop Signal Task (SSRT), are evident in a number of substance-dependent populations (Smith, Mattick, Jamadar, & Iredale, 2014) and may predict future problematic use. Conversely, inhibitory control deficits can be improved through computer-based training schedules, by adapting tasks such as the SSRT (Allom, Mullan, & Hagger, 2015) and similar results can also occur after CBT. Several studies have demonstrated the effectiveness of pharmacotherapies for addiction. Some evidence suggests that they influence inhibitory control although findings have been mixed, and opposite effects have emerged depending on baseline performance.  Field argued that in the future, inhibitory control (and other core dysfunctions) could be targeted by combining multimodal techniques in response to individual need.

David Baldwin presented data from an experimental inhalation procedure using air enriched with 7.5% carbon dioxide (CO2). In healthy volunteers, this paradigm mirrors the subjective, autonomic and cognitive features of Generalized Anxiety Disorder (Molina-Holgado, Amaro, González, Alvarez, & Leret). 7.5% CO2 inhalation demonstrates validity according to several pharmacotherapies (Bailey, Kendrick, Diaper, Potokar, & Nutt, 2007) including paroxetine, lorazepam, duloxetine, memantine and quetiapine. It is also sensitive to transcranial direct current stimulation, and psychological interventions such as mindfulness (Ainsworth et al., 2015). Baldwin concluded that the 7.5% CO2 model can produce replicable effects across a range of outcome measures and experimental manipulations, and may be a useful tool to evaluate novel psychological and pharmacological treatments for GAD.

Emily Holmes described her work on mental imagery, which plays a well-known role in Post-Traumatic Stress Disorder (PTSD) but also other conditions such as Bipolar Disorder. Following an analogue trauma event (a distressing film), healthy volunteers typically experience involuntary, intrusive memories that can be quantified across the following week. Using this paradigm, Holmes demonstrated that completing a visuospatial cognitive task (‘Tetris’) can interfere with both the stabilisation of new memories via consolidation (Holmes, James, Coode-Bate, & Deeprose, 2009) and the restabilisation of existing memories following their retrieval, via reconsolidation (James et al., 2015). Targeting reconsolidation could offer an exciting link between psychological and pharmacological treatments: it could offer lasting recovery from a range of disorders characterised by memory (e.g. PTSD, addiction, anxiety disorders), may be effective after a single retrieval procedure, and can be blocked by specific pharmacotherapies (Das, Freeman, & Kamboj, 2013).

Guy Goodwin began a panel discussion by drawing attention to the challenges of translating neuroscience to clinical advances. Historically, landmark discoveries in drug development have occurred through serendipity rather than translation (e.g. lithium, chlorpromazine and clozapine). Subsequently the divide between preclinical neuroscience and clinical psychopharmacology grew further; clinical trials were readily adopted using rigid psychiatric diagnoses and without a strong preclinical rationale. This hindered genuine innovation and made it difficult to distinguish a failed drug from a failed trial. Goodwin suggested that parallels could be drawn for psychological therapies, where major advances have been relatively recent (e.g. CBT and mindfulness) but divorced from neuroscience, despite its increasingly prominent role in other aspects of psychology.

The audience-led discussion in Bristol (BAP) focused on the need for improved neuroscience training in both clinical psychology and psychiatry. Baldwin noted that this has been a controversial part of psychiatric training; students learn a great deal of facts including neuroscience, but there is very little focus on retaining this knowledge afterwards (unless one joins an organization such as the BAP!) Holmes added that neuroscience is not yet a core part of clinical psychology training in the UK, although it is elsewhere (e.g. The Karolinska Institute, Sweden). On the other hand, perhaps neuroscience training will only be provided if and when it has a significant impact on mental health practice (Roiser, 2015).

Discussion of converging mechanisms in psychological and pharmacological treatments led to an interesting comment about adverse event reporting. Despite the rigorous procedures applied to drug trials, adverse events from psychological therapies are seldom considered. Indeed, many people (including ethics committees) reportedly believe that there is no such thing as a ‘side effect’ of therapy. Yet considering their possible mechanisms, it will be important to evaluate the potential adverse effects of talking therapies.

One issue that wasn’t touched upon was whether drugs could improve core components of psychological treatments. For example, ‘therapeutic alliance’ - the collaborative and affective bond between therapist and client, is a well-established predictor of outcome across different therapies (Martin, Garske, & Davis, 2000). Pharmacologically aiding therapeutic alliance could therefore be helpful in certain circumstances. Candidate drugs include 3,4-methylenedioxymethamphetamine (MDMA) although its medical use is currently restricted (Sessa & Nutt, 2015).

Improving mental health interventions will require interdisciplinary collaboration, substantial innovation, and regulatory challenges. Experimental medicine models (e.g. emotional bias, inhibitory control, 7.5% CO2 and analogue trauma) reveal common mechanisms in psychological and pharmacological treatments, and are ideally suited to investigate their synergy in a time- and cost- effective manner. As Goodwin argued, the moderate success of current treatments (Huhn et al., 2014) can be seen as a glass half-full or half-empty: far better than 50 years ago, but hopefully far poorer than our treatments will be in 50 years’ time.

References 

Ainsworth, B., Marshall, J. E., Meron, D., Baldwin, D. S., Chadwick, P., Munafò, M. R., & Garner, M. (2015). Evaluating psychological interventions in a novel experimental human model of anxiety. Journal of Psychiatric Research, 63, 117-122.

Allom, V., Mullan, B., & Hagger, M. (2015). Does inhibitory control training improve health behaviour? A meta-analysis. Health psychology review, doi:10.1080/17437199.17432015.11051078.

Bailey, J. E., Kendrick, A., Diaper, A., Potokar, J. P., & Nutt, D. J. (2007). A validation of the 7.5% CO2 model of GAD using paroxetine and lorazepam in healthy volunteers. Journal of Psychopharmacology, 21(1), 42-49.

Das, R. K., Freeman, T. P., & Kamboj, S. K. (2013). The effects of N-methyl D-aspartate and B-adrenergic receptor antagonists on the reconsolidation of reward memory: a meta-analysis. Neuroscience and Biobehavioral Reviews, 37(3), 240-255.

Harmer, C. J., O’Sullivan, U., Favaron, E., Rachel Massey-Chase, B., Ayres, R., Reinecke, A., et al. (2009). Effect of acute antidepressant administration on negative affective bias in depressed patients. The American journal of psychiatry, 166(10), 1178-1184.

Holmes, E. A., Craske, M. G., & Graybiel, A. M. (2014). A call for mental-health science. Nature, 511(7509), 287-289.

Holmes, E. A., James, E. L., Coode-Bate, T., & Deeprose, C. (2009). Can Playing the Computer Game" Tetris" Reduce the Build-up of Flashbacks for Trauma?: A Proposal from Cognitive Science. PLoS ONE, 4, e4153.

Huhn, M., Tardy, M., Spineli, L. M., Kissling, W., Förstl, H., Pitschel-Walz, G., . . . Davis, J. M. (2014). Efficacy of pharmacotherapy and psychotherapy for adult psychiatric disorders: a systematic overview of meta-analyses. JAMA psychiatry, 71(6), 706-715.

James, E. L., Bonsall, M. B., Hoppitt, L., Tunbridge, E. M., Geddes, J. R., Milton, A. L., & Holmes, E. A. (2015). Computer game play reduces intrusive memories of experimental trauma via reconsolidation-update mechanisms. Psychological science, doi:10.1177/0956797615583071.

Martin, D. J., Garske, J. P., & Davis, M. K. (2000). Relation of the therapeutic alliance with outcome and other variables: a meta-analytic review. Journal of Consulting and Clinical Psychology, 68(3), 438.

Molina-Holgado, F., Amaro, A., González, M. I., Alvarez, F. J., & Leret, M. L. (1996). Effect of maternal Δ 9-tetrahydrocannabinol on developing serotonergic system. European Journal of Pharmacology, 316(1), 39-42.

Reinecke, A., Waldenmaier, L., Cooper, M. J., & Harmer, C. J. (2013). Changes in automatic threat processing precede and predict clinical changes with exposure-based cognitive-behavior therapy for panic disorder. Biological Psychiatry, 73(11), 1064-1070.

Roiser, J. P. (2015). What has neuroscience ever done for us? The Psychologist, 28, 284-287.

Sessa, B., & Nutt, D. (2015). Making a medicine out of MDMA. The British Journal of Psychiatry, 206(1), 4-6.

Shiroma, P. R., Thuras, P., Johns, B., & Lim, K. O. (2014). Emotion recognition processing as early predictor of response to 8‐week citalopram treatment in late‐life depression. International Journal of Geriatric Psychiatry, 29(11), 1132-1139.

Smith, J. L., Mattick, R. P., Jamadar, S. D., & Iredale, J. M. (2014). Deficits in behavioural inhibition in substance abuse and addiction: a meta-analysis. Drug and Alcohol Dependence, 145, 1-33.