14 Corso di Aggiornamento della Societ Italiana di Neurologia ASPIRINA E DEMENZA: QUALI PROSPETTIVE

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Sorrento, 29 march 2008
Domenico Cassano Neuro-Psychiatrist
Primary headaches and psychiatric comorbidity in
a neurological territorial centre
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Headache and Psychiatric Comorbidity

• Well-recognized
• Misunderstood
• Clinically relevant
• Needing further systematic research

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well-recognized
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EPIDEMIOLOGICAL AND COMMUNITY STUDIES

• GREATER FREQUENCY OF PSYCHIATRIC DISORDERS
• AMONG RECURRENT HEADACHE PATIENTS
• THAN AMONG THE GENERAL
  POPULATION

• THE PREVALENCE OF PSYCHOPATHOLOGY
• INCREASES AND IS OVER REPRESENTED
• IN CLINICAL POPULATIONS
  

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PREVALENCEPD IN MIGRAINE
In large scale population-based
studies, migraineurs are more likely
to have Major Depression (OR
2.2 to 4.0) Bipolar disorders
(OR 2.9 to 7.3) ()
Generalized anxiety disorder (OR 3.5 to 5.3)
Panic disorder (OR 3.7)
Hamelsky SW, Lipton RB, 2006
() strong association with bipolar II
disorder
(Fasmer
et al, 2004)
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SIGNIFICANT GENDER DIFFERENCES IN COMORBIDITY

• WOMEN ARE SIGNIFICANTLY MORE LIKELY THAN MEN
• TO RECEIVE LIFETIME DIAGNOSES OF
• BOTH MIGRAINE (24 VS 9) AND MAJOR DEPRESSION
  (24 VS 13 ) BY AGE 30
• WITH RELATIVE FEMALE RISK INCREASING FOR MIGRAINE
  IN LATE ADOLESCENCE
• AND FOR MAJOR DEPRESSION AFTER ABOUT AGE 20

• LONGITUDINAL DATA INDICATE THAT RELATIVE TO MEN,
• WOMEN ARE
• FOUR-FOLD MORE LIKELY TO DEVELOP MIGRAINE
• AND TWO-FOLD MORE LIKELY TO DEVELOP MAJOR
  DEPRESSION

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SIGNIFICANTLY HIGHER PREVALENCE IN

• TRANSFORMED MIGRAINE ( 15 YEARS /- 5 )
• HIGH FREQUENCY OF ATTACKS
• MIGRAINE WITH AURA ()
• () Oedegaard KJ et al, 2006

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PREVALENCEPD IN TENSION - TYPE HEADACHE

• Increased frequency of psychiatric disorders
  (anxiety and depression) in pts. with TTH from
  three to 15-fold compared with healthy controls
• Psychiatric comorbidity is more frequent in
  chronic
• than episodic TTH pts.
• Depression is the psychiatric disorder most
  frequently
• associated with the headache
• Puca et al, 1999
• Holroyd
  et al, 2000

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PREVALENCE PD IN CHRONIC DAILY HEADACHE

• Mood disorders more frequent in pts. with chronic
• headache for more than 5 years
• ( 90 at least one psychiatric disorder
• 25 Major Depression
• 17 Dysthimia)
• Verri et
  al, 1998

Frequency of mood/anxiety disorders
significantly higher in pts. with chronic
migraine than in those with chronic
tension-type headache Juang
et al, 2000
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SYMPTOMATIC DOMAINS OF MIGRAINE AND LIFETIME
COMORBIDITY DISORDERS
The association M/MD applies to a broad age
range (Breslau et al, 2000)
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misunderstood
one of the most poorly understood Alvin E.
Lake, 2005
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SIGMUND FREUD
Association psychopathology / headache
Headache as symptom of unconscious
removed/repressed experiences
Karwautz et al, 1996
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migraine personality

• a medley of personality features and
  reactions dominant in individuals with migraine
  including feeling of insecurity
• with tension manifested as

• inflexibility, conscientiousness,
• meticolousness, perfectionism
• and resentment

HAROLD WOLFF (1937)
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Psychosomatic medicine

• Psychodynamic conceptualizations of migraine in
  psychopathological terms

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Multifactorial model of comorbid headaches
FACTORS
CLINICAL
BIOLOGICAL
PSYCHOLOGICAL
BEHAVIOURAL
SOCIAL
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How many headache clinicians or researchers are
prepared to dispute the significance of
psychological, behavioral, and social factors in
precipitating and exacerbating recurrent
headache disorders ?
Alvin E. Lake, 2005
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PATHOGENESIS OF THE RELATIONSHIP H/PD
CASUAL OR NOT-CASUAL ASSOCIATION ?

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EPIDEMIOLOGICAL CLINICAL GENETIC
EVIDENCES NEUROBIOLOGICAL BEHAV
IORAL CLOSE RELATIONSHIP
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PSYCHOPATHOLOGY OF HEADACHES
Bidirectional influences

PD
H
H
PD
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BIDIRECTIONAL RELATIONSHIP

• Migraineurs have a more than three-fold relative
  risk of developing depression compared with
  non-migraine patients (OR 3,2)
• Depression patients that have never suffered from
  migraine before have a more than three-fold risk
  of developing migraine compared with
  non-depressed patients (OR 3,1)
• 
  Breslau N et al, 2003

but specifical influences
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SPECIFIC RELATIONSHIP

• the presence of migraine or severe non-migraine
  headache increases a patients risk of developing
  depression disorders (OR 2.35) or panic attack
  disorder (3.55)
• whereas
• the presence of depression or panic attack
  disorder is associated with a greater risk
  of developing migraine (OR 2.75) , but not
  severe non-migraine headache (OR 1.85)
• Breslau et al 2003
  Torelli P, DAmico D, 2004

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LEARNED HELPLESSNES (Seligman, 1975)

• The psychological state that frequently results
• when events are uncontrollable.
• Depression in caused by the belief that action is
  futile.
• Recurrent disabling migraine attacks
• (generally unpredictable and uncontrollable)
• as learned helplessness
• Needing for cognitive-behavioural interventions

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• Shared neuropathic mechanisms

GENETIC RISK FACTORS
H
BRAIN STATE
ENVIRONMENTAL RISK FACTORS
PD

• NEUROPLASTIC PROCESSES
• IN CORTICOLIMBIC STRUCTURES

Sheftell FD, Atlas SJ, 2002
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Nociception-induced neuroplasticity at the
cortico-limbic level

• cross sensitization
• of sensory and affective components
  of pain

• 
  LAPS
• LIMBICALLY AUGMENTED PAIN SYNDROME
• The sensory/affective/behavioural
  symptom complex
• observed in subsets of chronic
  pain patients
• atypical and treatment - refractory pain
  complaints,
• disturbance of mood, sleep, energy,
  libido,memory/
• concentration, behaviour and stress
  intolerance.
• Rome et al, 2000
  Cady et al. 2005

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Cosensitization of the sensory and
affective components of pain
During and between episodes of headache (Chronic
Daily Headache)
other neurologic and psychologic symptoms

• Chronic migraine as a more pervasive
  neurologic disease in which the patients
  neurologic and psychologic function fails to
  return to a normal baseline

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clinically relevant
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DIAGNOSTIC PROGNOSTIC / OUTCOME THERAPEUTICAL
IMPLICATIONS
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MODIFIABLE RISK FACTORS FOR MIGRAINE
PROGRESSION(TRANSFORMED MIGRAINE)

• FREQUENCY OF MIGRAINE ATTACKS
• OBESITY
• ACUTE MEDICATION OVERUSE
• CAFFEINE OVERUSE
• STRESSFUL LIFE EVENTS
• DEPRESSION
• SLEEP DISORDERS
• Bigal ME, Lipton RB, 2006

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MIGRAINE OUTCOME
Negative outcome
Positive outcome
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PREDICTORS OF MIGRAINE OUTCOME
DSM-IV TR
MOOD DISORDERS
Nappi et al, modif., 2003
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HEADACHES AND PSYCHIATRIC COMORBIDITY(DSM IV TR)

• AXIS I
• AXIS II
• AXIS III CHRONIC DAILY HEADACHE
• TENSION-TYPE
  HEADACHE
• MIGRAINE

MOOD/ANXIETY DISORDERS
BORDERLINE PERSONALITY DISORDER
Increasing complexity and difficulty
More intensive multidisciplinary approaches
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PHARMACOLOGICAL THERAPY
ANTIDEPRESSANTS EFFICACY IN CHRONIC HEADACHE
PAIN
ANTIDEPRESSANTS
ANALGESIC EFFECT
ANTIEPILEPTIC DRUGS
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ANTIDEPRESSANTS CHOICING CRITERIAIN PREVENTIVE
TREATMENT OF COMORBID M/TTH MD
Specificity of antidepressants pharmacological
profile
Chemical structure of principles tricyclic,
heterocyclic, other
Clinical features of comorbid disorders
Biochemical profile serotoninergic and/or
noradrenergic
Involvement of opiate ?1, ? d , m receptors
3,
Dosage
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• BEHAVIOURAL APPROACH

• TYPE A MODIFICATION
• LOCUS OF CONTROL
• STRESS MANAGEMENT
• PATIENTS EDUCATION

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PSYCHO-THERAPEUTIC TREATMENT

• PSYCHOLOGICAL AID THERAPY
• FAMILIAR THERAPY
• SUPPORT GROUPS

Provide education Provide the patient with
the sense that they are non alone Opportunity to
share experiences and gain mutual
support Appropriate forum for family involvement

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needing further systematic research
clinically discussed far more often than
systematically studied
Silberstein, 1995
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Our experiencepreliminary data obtained by the
Mini International Neuro-psychiatric Interview
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ACCURATELY IDENTIFY AND CLASSIFY THE SUBSETS OF
HEADACHE PATIENTS WITH PSYCHIATRIC
DISORDERS
UTILIZE RELIABLE, VALID, STANDARDIZED DIAGNOSTIC
CRITERIA FOR HEADACHES AND PSYCHIATRIC DISORDERS
ICHD-2/ DSM-IV ICHD-2 Structured Headache
Interview MINI International Neuropsychiatric
Interview
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MINI

• Mini International Neuropsychiatric Interview a
  short, structured diagnostic interview, developed
  in 1990 by psychiatrists and clinicians in the
  United States and Europe for DSM-IV and ICD-10
  psychiatric disorders
• Administration time approximately 15 min.

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MAIN PSYCHIATRIC DISORDERS INVESTIGATED
AXIS II
AXIS I

• BORDERLINE PD

• ANXIETY DISORDERS
• PANIC DISORDER
• GAD
• DOC
• MOOD DISORDERS
• MAJOR DEPRESSION
• DYSTHIMIA
• BIPOLAR II DISORDER

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Sample of adult patients n. 96
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Depressive episode detected by MINI
59.9
69.6
68.3
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Anxiety disorder (GAD) detected by MINI
19.3
18.4
18.4
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Panic disorder detected by MINI
12.7
5.5
14.2
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DOC detected by MINI
2.3
1.3
9.4
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NEXT STEPS

• EVALUATE THE IMPACT OF PSYCHIATRIC DISORDERS ON
  HEADACHE SYMPTOMS AND TREATMENT
• IDENTIFY SPECIFIC INDIVIDUALIZED PHARMACOLOGIC,
  BEHAVIOURAL, PSYCHOTHERAPEUTIC TREATMENT
  STRATEGIES

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SPECIAL THANKS TO

• PASQUALE ALFIERI

• MICHELE FELEPPA

• ANEMOS STAFF
• GINA DONOFRIO
• M. ANTONIETTA AMATO
• M. ROSARIA PORCARO

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Thanks for attention
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SPECIAL THANKS TO
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(No Transcript)
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NEXT STEP
EMPLOY METHODS AND DESIGNS THAT

• UTILIZE RELIABLE, VALID, STANDARDIZED DIAGNOSTIC
  CRITERIA FOR HEADACHES AND PSYCHIATRIC DISORDERS
  (ICHD-2/ DSM-IV)
• ACCURATELY IDENTIFY AND CLASSIFY THE SUBSETS OF
  HEADACHE PATIENTS WITH PSYCHIATRIC
  DISORDERS
• EVALUATE THE IMPACT OF PSYCHIATRIC DISORDERS ON
  HEADACHE SYMPTOMS AND TREATMENT
• IDENTIFY OPTIMAL BEHAVIOURAL AND PHARMA-COLOGIC
  TREATMENT STRATEGIES

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PREVALENCE PD IN MIGRAINE

• Increased frequency of psychiatric
  disorders ( anxiety -
• mood disoders) in pts. with migraine (at
  least three-fold) compared with healthy
  controls
• Psychiatric comorbidity increases with
  increasing frequency and severity of headache
  (clinical samples of patients with
  migraine-related disorders and with medication
  overuse)

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THE FIRST STEP

• UTILIZE RELIABLE, VALID, STANDARDIZED DIAGNOSTIC
  CRITERIA FOR HEADACHES AND PSYCHIATRIC DISORDERS
  (ICHD-2/ DSM-IV)
• ACCURATELY IDENTIFY AND CLASSIFY THE SUBSETS OF
  HEADACHE PATIENTS WITH PSYCHIATRIC
  DISORDERS
• EVALUATE THE IMPACT OF PSYCHIATRIC DISORDERS ON
  HEADACHE SYMPTOMS AND TREATMENT
• IDENTIFY OPTIMAL BEHAVIOURAL AND PHARMA-COLOGIC
  TREATMENT STRATEGIES

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NEXT STEP
EMPLOY METHODS AND DESIGNS THAT

• UTILIZE RELIABLE, VALID, STANDARDIZED DIAGNOSTIC
  CRITERIA FOR HEADACHES AND PSYCHIATRIC DISORDERS
  (ICHD-2/ DSM-IV)
• ACCURATELY IDENTIFY AND CLASSIFY THE SUBSETS OF
  HEADACHE PATIENTS WITH PSYCHIATRIC
  DISORDERS
• EVALUATE THE IMPACT OF PSYCHIATRIC DISORDERS ON
  HEADACHE SYMPTOMS AND TREATMENT
• IDENTIFY OPTIMAL BEHAVIOURAL AND PHARMA-COLOGIC
  TREATMENT STRATEGIES

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METHODS

• STRUCTURED INTERVIEW FOR HD

• ICHD-II

• MINI

DSM-IV

• (Mini International Neuropsychiatric Interview),
  a short, structured diagnostic interview,
  developed in 1990 by psychiatrists and clinicians
  in the United States and Europe for DSM-IV and
  ICD-10 psychiatric disorders. 
• Administration time approximately 15 min.

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ANTIDEPRESSANTS CHOICING CRITERIAIN PREVENTIVE
TREATMENT OF COMORBID M/TTH MD
Clinical features of comorbid disorders
Specificity of antidepressants pharmacological
profile
Chemical structure of principles tricyclic,
heterocyclic, other
Biochemical profile serotoninergic and/or
noradrenergic
Involvement of opiate ?1, ? d , m receptors
3,
Dosage
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ANTIDEPRESSANTS AVAILABLE ON MARKET
ANTIDEPRESSANTS EFFICACY IN CHRONIC HEADACHE
PAIN
TRICYCLIC
SSRI
documented by controlled studies -
methodological limits -
SNRI
MAO-I
NARI
NASSA
RIMA
ANALGESIC EFFECT
Trazodone, Nefazodone, Bupropion
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a close relationship between migraine and
mood-disorders exists

• Merikangas et al (1990, 1993)
• Breaslau et al (1991, 1994, 2000, 2001)
• Lipton et al (2000)
• Wang et al (1999)

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ANTIDEPRESSANTS CHOICING CRITERIAIN PREVENTIVE
TREATMENT OF COMORBID M/TTH MD
Clinical features of comorbid disorders
Specificity of antidepressants pharmacological
profile
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ANTIDEPRESSANTS CHOICING CRITERIAIN PREVENTIVE
TREATMENT OF COMORBID M/TTH MD
Clinical features of comorbid disorders
Specificity of antidepressants pharmacological
profile
Chemical structure of principles tricyclic,
heterocyclic, other
Biochemical profile serotoninergic and/or
noradrenergic
Involvement of opiate ?1, ? d , m receptors
3,
Dosage