Do drugs help or hinder psychological therapy?

1. Do drugs help or hinder psychological therapy? By Joanna Moncrieff, Senior Lecturer, UCL. July, 2008, Declaration of interests: Critical Psychiatry Network

4. Psychoactive drugs • Produce altered mental states • Tolerance • Withdrawal effects • “spell binding” (Breggin, 2007)

5. barbiturates hysocine paraldehyde opium bromides benzedrine amphetamine thyroxine (sex hormones) Drugs used prior to 1950s

7. Insulin coma therapy “the introduction of insulin coma treatment was from a historical point of view the decisive step from a purely symptomatic to a curative therapy of the endogenous psychoses.” Ehrhardt, 1966

9. ECT and depression • “ a specific and adequate means to relieve this common illness” (involutional melancholia) (Moss et al, 1953). • Stimulated an underactive pituitary gland (Sadler, 1953) • Rectified abnormal brain circuits (Paterson, 1963)

10. Kilogrammes of Chlorpromazine used in French Hospitals 1952-1957 (J.Swazey, 1974)

11. Specificity of neuroleptics • “they appear to do more than tranquilise” (Henderson & Gillespie 1962). • “the drugs penetrate much closer to the site of mechanism of the disease itself than any other procedure applied hitherto” (Mayer-Gross, Slater, & Roth 1960).

12. NIMH trial of acute treatment in schizophrenia, 1964 “the phenothiazines should be regarded as ‘antischizophrenic’ in the broad sense. In fact it is questionable whether the term ‘tranquilizer’ should be retained.” NIMH 1964

15. Pre 1950s: Sedatives Stimulants Post 1950s: Antipsychotics Antidepressants Anxiolytics Mood stabilisers Hypnotics Treatment resistant psychosis Changes in Therapeutic Concepts

16. Evidence for disease centred model • NOT placebo controlled trials • If the pathology of the disease explains drug action • If non specific drugs are inferior • If healthy volunteers do not show the “therapeutic” effects • If animal tests select specific drugs • If outcomes improve

17. Pathology of psychiatric conditions unknown • Dopamine hypothesis of schizophrenia and monoamine hypothesis of depression derived from knowledge of drug action • No conclusive independent evidence for them

18. Evidence against the dopamine hypothesis of schizophrenia (Moncrieff, in press Harvard review of Psychiatry) • Studies of dopamine activity in psychotic patients vs controls have not controlled for other factors associated with dopamine activity and release such as movement, stress, attention, arousal and sometimes previous drug treatment. Results are inconsistent anyway • Atpypical antipsychotics like clozapine have relatively low D2 blocking activity • Stimulant induced psychosis has not been pinned down to dopamine- other NTs likely to be involved

19. Are neuroleptics superior to other sorts of sedatives? • Barbiturates: 2 early studies showedchlorpromazinesuperior • Opium: 1 study. Opium equal to chlorpromazine for acute psychosis • Benzodiazepines: 6 trials: 3 trials AP=BZD; 2 trials BZD>AP; 1 trial CPZ<BZD=HAL • Lithium: equal in moderately active cases, inferior in overactive cases (Braden et al, 1980).

21. A hospital study (Baldessarini et al, 1995) • 84% of patients on neuroleptics on at least one other CNS depressant type of drug (mostly benzodiazepines and anticonvulsants), 45% on more than one other

22. Drugs that “improve” depression in clinical trials • Buspirone • Amphetamine • Ritalin • Alprazolam • Diazepam • Thioridazine (Melleril) • Reserpine • Other antipsychotics • Dihydrocodeine • Hypericum (St Johns wort)

23. Lithium • Never shown to be superior to other sedatives (neuroleptics, benzodiazepines) for treatment of mania • No specificity for affective disorders (Johnstone et al, 1980; Braden et al, 1983). • Other sedative drugs also used as prophylactics, e.g. olanzapine and anticonvulsants

24. No evidence that any class of drug used in psychiatry has a disease centred effect • Therefore we have to assume that they act in a drug centred manner • This requires a complete overhaul of the way we approach drug use

25. Do neuroleptics improve the outcome of psychosis and schizophrenia? • Hegarty et al, 1994: outcome of schizophrenia in 1990s same as that in 1930s • Robinson et al, 2004: only 14% FE patients made a full recovery • Tiihonen et al, 2006: FE patients had an average of 2 readmissions in 3.6 yrs • Better outcome in developing world?

26. Outcome without neuroleptics: • Soteria project: 30% psychosis patients treated sucessfully without neuroleptics • Letinen et al, 2000; 43% psychosis patients treated without neuroleptics • Studies show patients who do not use neuroleptics have a better outcome. E.g. Harrow et al, 2007: 40% using no medication recovered vs 5-17% of patients using neuroleptics.

27. A drug centred approach: some drug-induced psychic effects • Euphoria • Sedation- different types • Emotional flattening • Relaxation • Stimulation • Psychedelic effects • Cognitive slowing and impairment • Reduced emotional sensitivity

28. A drug centred approach to treating psychosis • Sedation often required- may be the main point of treatment • Drugs that reduce mental activity and emotional reactions might be useful (neuroleptics – but also others) • But…balance of benefit to harms needs consideration • ?? Long-term prophylactic treatment may not be justified

29. Older neuroleptics from a drug centred perspective • Create a Parkinson disease-like state with reduced movement and thought and flattening of emotions • “Deactivation” (Breggin) • Also akathisia and discomfort • ? Brain damage- some studies show brain shrinkage (Lieberman et al, 2005 and others). Also TD and cognitive impairment.

30. Healthy volunteer studies • Antipsychotics reduce movement, attention, reaction times, co-ordination, intellectual abilities, and memory in volunteers. Subjective effects are sedation and emotional flattening, indifference and reduced initiative (Healy & Farquhar, 1999)

31. Atpyical antipsychotics • New drugs also produce produce a state of sedation, lethargy, flattened emotions and loss of interest. Associated with increased appetite and metabolic changes in some cases.

32. Askapatient.com • “I was eating and eating and sleeping and sleeping and sometimes I managed to do both at the same time” (Olanzapine)

33. Askapatient.com • “extremely hard to move, think, talk” (haloperidol) • “heavy mental and physical stagnance” (haloperidol)

34. Askapatient.com • “emotionally empty, dead inside” (trifluoperazine) • “oblivious to my surrounds…all creativity was squashed” (trifluoperazine) • “took away my sense of humour” (trifluoperazine)

35. Askapatient.com • “no emotions, only a weird, spacey, empty feeling, no arousal, no excitement, no joy, nothing” (risperidone)

36. Askapatient.com • “mental nothingness, a numbness that was unsettling” (risperidone) • “no thoughts or inner world” (risperidone)

37. Askapatient.com • “I’ve never been able to eat as much as I did when I was on Zyprexa. I gained 40lbs in no time and my mind was in a constant fog of lethargy and indifference. I didn’t care about anything. I just wanted to sit around and eat.” (olanzapine)

38. Askapatient.com • “decreased the intensity of inner voices” (risperidone) • “stops my negative thoughts and feelings being amplified and overwhelming me” (risperidone)

39. Askapatient.com • “hypersomnia (increased sleeping), calming of moods, general smoothing out of mania, calmness, less hallucinations” (olanzapine). • “it makes me feel like a veggie, but that was better than what I was going through and it kept me out of the hospital” (olanzapine)

40. Askapatient.com • “Although I felt very well, I felt as if I had absolutely nothing to talk about. I kept wondering about whatever [it] was that had been so interesting during most of my life that I had suddenly lost… But I was very much in contact with reality and for that I was thankful” (haloperidol)

41. Peter Wescott, BMJ, 1979 “…I must keep on with my injections” but.. “Unfortunately my personality has been so stifled that sometimes I think the richness of my pre-injection days- even with brief outbursts of madness-is preferable to the numbed cabbage that I have become”

42. A drug-centred perspective on use of psychiatric drugs • Psychiatric drugs are psychoactive drugs • They put people into altered, drug-induced states • We should assume they do more harm than good unless “proved” otherwise • They may suppress symptoms in short-term, but over longer-term body may counteract these effects • Stopping them may produce its own psychiatric problems related to withdrawal • Assumption of harm • “I was sane, but I was not much better off” comment on Askapatient.com

43. “Biopsychiatric treatments are deemed effective when the physician and/or the patient prefers a state of diminished brain function, with its narrowed or shallower range of mental capacity or emotional expression” (Breggin, 2008)

44. Animal models of psychosis • E.g. Conditioned Avoidance Response (CAR) and reduction of stimulant induced stereotypies • CAR response also obtained with benzos, histamine and toxins • Suppression of stimulant induced stereotypy is a test for dopamine antagonism • Some TCAs have stereotypy suppressing ability (esp. amitripytline and clomipramine). Atpycials have lower stereotypy suppressing ability

45. Lithium • Effects on a continuum with toxic effects- sedation, cognitive impairment and dysphoria in volunteers

46. Antidepressants as psychoactive drugs TCAs: chemically related to neuroleptics and similar effects in volunteers. Highly sedating.Cognitive and motor impairment, EEG slowing, dysphoria SSRIs: uncertain effects. No profound effects in volunteers except mild dysphoria and cognitive impairment at higher doses. Agitation in some.Possible emotional blunting