Tripartite Model, Psychopharmacology and the

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Tripartite Model, Psychopharmacology and the
Other Face of Depression

• Dr Khalid Mansour
• Locum Consultant Psychiatrist
• Radbourne Unit - Derby

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(No Transcript)
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• The other face of depression, reduced positive
  affect the role of catecholamines in causation
  and cure
• David Nutt University of Bristol
  Psychopharmacology Unit, Bristol, UK.
• Koen Demyttenaere UZ Gasthuisberg, Adult and
  Geriatric Psychiatry, Belgium.
• Zoltan Janka Department of Psychiatry, University
  of Szeged, Hungary.
• Trond Aarre Nordfjord Psychiatric Centre,
  Sjukehusvegen.
• Michel Bourin Faculté de Médecine Pharmacologie
  Clinique, France.
• Pier Luigi Canonico Department Facoltà di
  Farmacia, Università del Piemonte Orientale,
  Italy.
• Jose Luis Carrasco Department of Clinical
  Psychiatry, U. Complutense de Madrid, Hospital
  Universitario Clinico San Carlos de Madrid,
  Spain.
• Steven Stahl Neuroscience Educational Institute,
  California, USA.

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Tripartite Model and Psychopharmacology Summary

• Tripartite modal was developed mainly in the
  context of research in clinical psychology to
  create better self assessment questionnaires for
  both anxiety and depression. In such
  questionnaires differentiating anxiety from
  depression can be difficult.
• One of the basic concepts of such research models
  has been that our every day affect is really the
  outcome of mixing two different affects Positive
  Affects (PA) and Negative Affects (NA).

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Tripartite Model and Psychopharmacology Summary

• PA positive mood states, e.g. happiness (joy),
  interest, energy, enthusiasm, alertness and
  self-confidence.
• NA distress mood states, e.g. fear, anxiety,
  sadness, irritability, loneliness, guilt, disgust
  and hostility.

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Tripartite Model and Psychopharmacology Summary

• Psychiatric studies seems as if it had ignored
  such psychological research for a long time (most
  research done by psychologists).
• However, recent developments in
  psychopharmacology have increased interest in PA
  and NA as a way to refine treatment of
  depression.
• This new approach has been increasingly popular
  among psychiatrists in the USA and UK.

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Two-Factor Structure of Affect

• The Tripartite Model of anxiety and depression is
  part of a long tradition of the study of emotions
  (e.g., Izard, 1972 Tomkins, 1962, 1963,
  Davidson, 1992, 1998 Gray, 1994). One common
  feature of these models is the emphasis on the
  Two-Factor Structure of Affect (Shankman
  Klein, 2003).
• Two-Factor Structure of Affect emotions fall
  along two dimensions Positive Affect (PA) and
  Negative Affect (NA) (ZevonTellegen, 1982) .

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Three-Factor Structure of Affect

• The three-factor theories like the tripartite
  model tend to add to the PA-NA structure an
  extra structure to explain other mood
  abnormalities especially anxiety disorder,
  phobia, OCD, etc (Shankman Klein, 2003).

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Three-Factor Structure of Affect

• Tripartite Model adds Arousal (Watson Clark,
  1984Watson Tellegen, 1985).
• Approach-withdrawal Model (Davidson, 1992, 1998).
• Behavioural Activation System (Carver White,
  1994).
• Behavioural Facilitation System (Depue Iacono,
  1989).
• Valence-Arousal Model adds Arousal/Anxious
  Apprehension (AA) (Heller et al, 1995,1997
  Heller Nitchke, 1998).
• Grays three system model (Gray, 1994)
  Behavioural Approach System, Behavioural
  Inhibition System and Fight/Flight System.

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Tripartite Model Negative Affect (NA)

• NA a broad general factor of emotional distress,
  that includes moods such as fear, sadness, anger,
  and guilt (Watson Clark, 1984Watson Tellegen,
  1985) and so it is a common feature of both
  anxiety and depression.
• Traditional self-report measures of depression
  and anxiety are tapping NA (Laurent Ettelson,
  2001).
• Separating depression from anxiety dependes on PA
  (Laurent Ettelson, 2001).

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Tripartite Model Positive Affect (PA)

• PA pleasurable engagement with the environment
  (Watson, 1988 Watson Tellegen, 1985) including
  happiness, interest, energy, enthusiasm,
  alertness and self-confidence.
• Depression is characterized by low PA i.e.
  Anhedonia.
• In anxiety, levels of PA are not significantly
  different than those expected in the general
  population.

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Tripartite Model PA and NA

• Some believe that PA and NA are bipolar or
  represent opposite ends of a continuum (e.g.,
  Feldman Barrett Russell, 1998, 1999 Russell,
  1980 Russell Feldman Barrett, 1999).
• Most believe that PA and NA represent independent
  constructs (e.g., Watson Clark, 1997 Watson
  Tellegen, 1985 Watson, Wiese, Vaidya,
  Tellegen, 1999).
• This is the view adopted in psychopharmacology
  researches.

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The Tripartite Model Anxiety and Depression

• Clark and Watson (1991) concluded that data about
  anxiety and depression, were best captured by a
  tripartite structure.
• Non-specific distress factor (NA) is common to
  both anxiety and depression.
• Specific factor of low (PA) is characteristic
  for depression.
• Specific factor elevated physiological
  hyperarousal (PH) is characteristic for anxiety

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Tripartite Model Assessment Tools

• Several assessment tools have been developed
  based on the tripartite model e.g.
• Positive and Negative Affect Schedule (PANAS)
  (Watson, Clark, and Tellegen, 1988)
• Mood and Anxiety Symptom Questionnaire (MASQ)
  (Watson et al, 1995).
• Depression Anxiety stress Scale (DASS) (Lovibond
  Lovibond, 1995).

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Psychopharmacological Research and the Tripartite
Model

• Since the 1960s, with TCA, it has been recognized
  that norepinephrine (NE) and dopamine (DA) play
  an integral part in the underlying
  pathophysiology of depression (Willner, 1995
  Delgado, 2000, 2004 Nutt et al, 2006 Stahl,
  2009). Many of the TCA were causing exactly such
  effect.
• Since the late 1980s, SSRIs started to be widely
  used as the first-line therapy for the treatment
  of major depression especially in the primary
  care environment due to their improved safety
  profile and general ease of administration (Nutt
  et al, 2006).

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Psychopharmacological Research and the Tripartite
Model

• However, a substantial proportion of patients
  fail to respond to SSRI therapy (2855)
  (Nierenberg et al., 1999, Nierenberg and DeCocco,
  2001 Peterson et al., 2005 Trivedi et al.,
  2006).
• Even then 30-50 of the responding patients
  continue to experience residual symptoms
  (Fawcett, 1994 Bothwell Scott, 1997
  Nierenberg et al, 1999) such as sleep
  disturbances, diminished pleasure, loss of
  interest, fatigue or loss of energy and decreased
  motivation (i.e. low PA) (Kopta et al., 1994
  Barkham et al., 1996 Opdyke et al., 19961997
  Nierenberg et al., 1999 Shelton and Tomarken,
  2001).

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Psychopharmacological Research and the Tripartite
Model

• In the mean time, preliminary evidence suggested
  that antidepressants that enhance noradrenergic
  and dopaminergic activity may afford a
  therapeutic advantage over serotonergic
  antidepressants in the treatment of symptoms like
  those of low PA e.g. loss of interest, loss of
  energy and loss of motivation, (Bremner et al.,
  1984 Rampello et al., 1991 Dalery et al., 1997
  Jouvent et al., 1998 Jamerson et al., 2003
  Papakostas, 2006 Jefferson et al., in press).

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Psychopharmacological Research and the Tripartite
Model

• Eminent psychopharmacologists e.g. Professor Nutt
  and Professor Stahl started to suggest the usage
  of PA and NA concepts for prescribing
  antidepressants (Nutt et al, 2006 Stahl 2009)
• Depressed patients with dominant low PA need to
  be treated with drugs which enhance levels of DA
  and NA e.g. SNRI
• Depressed patients with dominant high NA need
  to be treated with drugs which enhance levels of
  5HT e.g. SSRI.

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Neurobiological Model of Depression (Nutt et al,
2006)
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Neurobiological Model of Depression (Nutt et al,
2006) Criticism

• Many psychological studies dispute the
  sufficiency and/or validity of the Tripartite
  model and found it not able to explain many
  aspects of depression and anxiety (Lonigan et al,
  1994 Clark et al, 1994 Burn Edison, 1998
  Buckby et al, 2008).
• Including guilt, sadness, irritability, fear,
  anxiety, etc, in one category NA, does not make
  much sense from clinical point of view.

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Neurobiological Model of Depression (Nutt et al,
2006) Criticism

• Many patients are still having limited response
  to both SSRI and SNRI (SNRI advantage over SSRI
  NNT24) (Papakostas et al, 2006)
• Including Nor-adrenaline in both PA and NA in
  Nutts model, does not make sense, chemically, as
  Nor-adrenaline system seems to be as independent
  system as 5HT and Dopamine.

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Neurobiological Model of Depression (Nutt et al,
2006) Criticism

• Nutts model needs further development.
• Nutts model does not involve environmental
  factors in either causing or treating depression.
  
• This model does not explain other major chemical
  transmitters in the brain e.g. glutamte, glycine
  or acetylcholine.

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Neurobiological Model of Depression (Nutt et al,
2006) Importance

• Add one extra dimension for better assessment and
  treatment of depression for the first time in
  about 60 years.
• It brings psychiatrists one step further to the
  promised Neurobiological Psychiatry (Bullmore et
  al, 2009 Craddock et al, 2008 St John-Smith et
  al, 2009)

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Neurobiological Model of Depression (Nutt et al,
2006) Importance

• It has many clinical applications e.g.
• Patients with ? PA better avoid anti
  dopaminergic drugs as augmentation therapy for
  treatment of depression.
• Fluoxetine can be considered superior SSRI as it
  also enhances Dopamine and Nor-adrenaline.
  Sertraline and Paroxetine enhance dopamine.
• Concepts of PA or NA can also be used in
  behavioural therapy and psychotherapy.

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Thank you

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