14. Psychopharmacology for Pain Medicine

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14. Psychopharmacology for Pain Medicine

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EPIDEMIOLOGY

• Pain clinic population? 6080? DSM criteria?
  ???? psychiatric illness ???.
• Major depression (3050), anxiety disorder,
  personality disorders, somatoform disorders, and
  substance use disorders.
• Major depression , anxiety disorders
• -M/C, medication? best response
• Psychiatric illness improvement
• 1) pain level? ??
• 2) pain? ???? ?? acceptance ??
• 3) functionality ??
• 4) ?? ? ??

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PSYCHIATRIC NOSOLOGY

• DSM-?, ICD-10 Psychiatirc diagnosis? ?? outline
  ? ??, reliability? ??.
• In this light, and in an attempt to demystify
  psychiatiric diagnosis for the pain physician,
  the following description of psychopathology will
  emphasize the hallmark feature of each illness.

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MAJOR DEPRESSION AND SUBTHRESHOLD DEPRESSION

• Symptom
• Treatment
• 1)Selective serotonin reuptake
  inhibitor(SSRIs)
• 2)Tricyclic antidepressants(TCAs)
• 3)Serotonin-Norepinephrine reuptake inhibitors
• (SNRIs)
• 4)Other antidepressants
• buproprion, mitrazapine,Trazodone and
  nefazodone
  

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Symptom
MAJOR DEPRESSION AND SUBTHRESHOLD DEPRESSION

• Situational depression? ???
• 1) Persistently low mood feeling blue, down,
  or depressed. Anhedonia, or the inability to
  experience pleasure
• 2) Self attitude change thoughts of guilt or
  thinking that one is a bad person.
• 3) Change in vital sense sleep, appetite, or
  energy level? ??.(??? 2??? ??)
• Becks triad Hopless, Hapless, and helpless
• Suicidal thought severity of depressive
  symptom.
• Major depression serious complication of
  persistent pain, and if not treated effectively
  it will reduce the effectiveness of all pain
  treatment.

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Treatment
MAJOR DEPRESSION AND SUBTHRESHOLD DEPRESSION

• All antidepressants take 2 to 4 weeks to see a
  clinical improvement.
• Initial depressive episode treatment 6 to 12
  months
• Recurrent depressive episode treatment 5years
• 60 pt. will respond to the initial
  antidepressant prescribed.
• Pain pt. with major depression have increased
  treatment resistance, particularly when their
  pain is not effectively managed.
• Older adults lower doses of antidepressants,
  high sensitivity to side effects and toxicity.
• Starting antidepressant begin with ¼ to ½ of
  standard initial treatment dose for a week, and
  then advance gradually over the next 2 to 3 weeks
  to the treatment dose.

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Treatment
MAJOR DEPRESSION AND SUBTHRESHOLD DEPRESSION

• Selective serotonin reuptake inhibitors(SSRIs)
• fluoxetine blockade of the presynaptic
  serotonin reuptake pump in the CNS.
• Antidepressant efficacy and low side effect
  most widely prescribed
• Few independent pain properties.
• Dosage one-half of usual dose for a week and
  then to the standard dose
• Side effect nausea, diarrhea, tremor, and
  headache. Sexual S/E (15libido?, impotence,
  ejeculatory disturbance, or anorganism)
• Metabolism Hepatic oxidation? ??. Cytochorome
  P450 enz.? induce and/or inhibit ??? ??? ??
  ??? serum level?????. (carbamazepine, lithium,
  antipsychotics and a commonly used analgesics,
  methadone)
• Discontiuation Tapered down slowly to avoid a
  withdrawal syndrom.(Headache, nausea, diarrhea,
  or myalgia)

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Treatment
MAJOR DEPRESSION AND SUBTHRESHOLD DEPRESSION

• TCAs oldest classes of andtidepressants.
• Mechanism Act by inhibiting both serotonergic
  and noradrenergic reuptake.
• Analgesic properties independent of their
  treatment effects on depression-diabetic
  neuropathy pain, chronic regional pain syndrome,
  chronic headache, posttroke pain, and
  radiculopathy
• Side effect anticholinergic and antihistamine
  effect, decreased seizure threshold. Quinidine
  like properties(proarythmic, prolong the QTC
  interval)
• Serum plasma level can be mornitored for TCAs.
  Laboratory screening of electrolytes, BUN,
  creatinine, and LFTs.

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Treatment
MAJOR DEPRESSION AND SUBTHRESHOLD DEPRESSION

• Metabolism strongly protein-bound and undergo
  1st-pass hepatic metabolism.
• P450 enz. Involve
• Inc. TCA plasma level SSRI, cimetidine,
  and
• 
  methylphenidate
• Dec. TCA plasma level phenobarbital,
• carbamazepine, and
  cigarette smoking
• Dosage begin at lower doses (25mg for a week)
  than the target doses for antidepressant
  effect(75-150mg)
• Analgesic effect dose 25-50mg
• antidepressant effect 75-150mg
• Withdrawl sx fever, sweating, headache, nausea,
  dizziness, or akathesia

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Treatment
MAJOR DEPRESSION AND SUBTHRESHOLD DEPRESSION

• Serotonin-Norepinephrine reuptake
  inhibitors(SNRIs) Venlafaxine and duloxetine
• Mechanism Inhibiting serotonin and
  norepinephrine reuptake. no alpha-1 cholinergic,
  or histamine inhibition.
• Superior analgesic properties of TCAs(NMDA
  antagonism and sodium ch. Blockade) neuropathic
  pain- higher dose of venlafaxine that appear to
  be needed for analgesic efficacy.
• Dosage beginning at 37.5mg per day for a week
  and then slowly incre. to as high as 375mg per
  day. Typical dose is 150-225mg.
• Side effect nausea, somnolence, dry mouth,
  dizziness, nervousness, constipation, anorexia,
  or sexual dysfunction.
• Caution doses over 150mg, increase SBP 10mmHg
  or more.( norepinephrine reuptake inhibition )

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Treatment
MAJOR DEPRESSION AND SUBTHRESHOLD DEPRESSION

• Other antidepressants
• Buproprion
• Mechanism noradrenergic and dopaminergic
  reuptake pump inhibitor
• Significant psychostimulant properties
  depression, ADHD, smoking cessation
• Independent analgesic effects in a neuropathic
  condition, effective in alleviating the sedative
  effects of opioid.
• Dosage start at 75-100mg in the morning.
  Advanced to the average treatment dose of
  100-150mg bid for 5 days.
• S/E seizure (450-600mg per day) nervousness,
  headache, irritability, and insomnia

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Treatment
MAJOR DEPRESSION AND SUBTHRESHOLD DEPRESSION

• Mirtazapine
• Mechanism antagonism of serotonin and central
  presynaptic alpha2-adrenergic receptor,
  stimulating serotonin and norepinephrine release.
• Dosage lower doses 15-30mg/day,(sedating,
  antianxiety effect) higher doses 45-60mg/d ( more
  activating, provoke anxiety sx.)
• S/E weight gain, agranulocytosis and
  neutropenia.
• Trazodone and nefazodone
• Mechanismserotonin-2 antagonist/reuptake
  inhibitors
• Ix major depression and insomnia
• Dosage sleep ( 25-100mg at bedtime ) depression
  ( 50-600mg/d bid)
• S/E priapism, sedation, dizziness, dry mouth,
  orthostatic hypotension, constipation, and
  headache.

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ANXIETY DISORDER

• Symptom
• Generalized anxiety(m/c), panic disorder, OCD,
  and PTSD
• Biological component responsive to medication.
• Pathological anxiety interfere normal
  funtioning(restless, fatigued, irritable, and
  poor concentration)
• Trait anxiety excessive worry and concern about
  routine matter. Great difficulty controlling
  worry
• Situational anxiety anxiety about pain and its
  negative consequences. Anxiety amplifies pain
  perception and pain complaints.

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Treatment
ANXIETY DISORDER

• Antidepressant
• 2-4weeks to see improvement.
• Dose ??? very slowly?? ???? ?.
• Diminish the overall level of anxiety , prevent
  anxiety or panic attacks.( no role in treating
  acute anxiety)
• SSRI greater anxiolytic properties
• TCAs OCD
• Mirtazapine anxiolytic properties,
• Buproprion depression with anxious feature.
• SNRIs generalized anxiety.

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Treatment
ANXIETY DISORDER

• Benzodiazepines(BZDs) and Buspirone
• IxAcute anxiety, panic attack, generalized
  anxiety.
• Acute anxiety or panic attack short acting BZDs
  (lorazepam 0.5-2mg q6hr)
• Clonazepam 0.25-2mg tid ( long acting BZD )
  persistent anxiety, prevent acute anxiety attacks
• S/E profound sedation, confusion, or resp.
  depression, fatal in overdose. Addictional
  potential.
• Physiological and psychological dependency (
  tapering from 1-3mon.) if not, insomnia, anxiety,
  delirium, psychosis, or seizures.
• Buspirone acute anxiolytic. No addictive
  properties.

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MOOD STABILIZERS

• Antimanic and antidepressant properties.
• Bipolar disorder.
• Lithum and valproic acid
• Lithium
• Ix major depressive disorder, prophylaxis for
  chronic daily headaches and cluster headaches
• Narrow therapeutic range serum level ??.
  Thyroid and kidney? ?? must be monitored.
• Sparse analgesic effect

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MOOD STABILIZERS

• Valproic acid
• Duration of action 8-12hr.
• Ix Antimanic and antidepressant effects.
  Migraine prophylaxis. Seizure treatment
• Dosage start 250mg/d typical dose in pain is
  250mg tid. Bipolar disorder 500-1000mg tid.
• Therapeutic and toxicity range serum level
  monitored
• CBC and LFT done.
• S/E thrombocytopenia (??? 2?? ??? platelet
  check) sedation, dizziness, hepatitis.

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NEUROLEPTICS

• Antipsychotics. schizophrenia and psychotic sx
  in depression, mania, or delirium.
• Independent pain properties
• Serious S/E Parkinsonism and tardive dyskinesia
• Typical neuroleptics(Haloperidol)
• Atypical neuroleptics(Clozapine)

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Typical neuroleptics

• Haloperidol molecular structure similar to
  morphine
• Mechnism Antagonism of dopamine receptors(D2)
• Side effect
• 1) anticholinergic S/E
• 2) extrapyramidal effect tremor, dystonia,
• akathesia, and most seriously tardive
• dyskinesia(permanent),
• 3) lower the seizure threshold
• 4) elevate serum glc.level
• 5) Cardiovascular effect
  hypotension,tachycardia,
• nonspecific EKG change(Torsades de
  Points)
• sudden cardiac death

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Atypical Neuroleptics

• Clozapine
• Mechnism lesser degree of D2R antagonism and
  greater degree of D4R antagonism , some degree of
  serotonin-2 R blocking.
• Caution DM pt lower glc. Tolerance, elevate
  serum glc.
• Ix
• 1) Effective for the positive
  symptoms(Hallucination and delusion), more
  effective for the negative symptoms(flat affect,
  poor motivation, and social withdrawl).
• 2)Treatment-resistant depression or anxiety.
• 3) Pain medicine secondary and tertiary
  agents for
• migraine and chronic daily headache
  prophylaxis.
• Cluster headache, cancer pain, thermal
  pain.
• S/E tardive dyskinesia (initial dose very low
  with a slow escalation)

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CONCLUSION

• 60 to 80 pt. with chronic Pain have significant
  psychiatric pathology.
• Antidepressant, anticonvulsant, and
  antipsychotics are the notable for their pain
  properties.
• Psychotherapeutic medication result in
  significantly improved treatment.
• The improved Tx result for psychopathology and
  the emergence of additional analgesics is a boon
  to pain medicine practice.