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14. Psychopharmacology for Pain Medicine

14. Psychopharmacology for Pain Medicine. 경희의료원 마취통증의학과 R2 전주연. EPIDEMIOLOGY. Pain clinic population 의 60~80% 는 DSM criteria 를 충족하는 psychiatric illness 갖는다 . Major depression (30~50%), anxiety disorder, personality disorders, somatoform disorders, and substance use disorders.

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14. Psychopharmacology for Pain Medicine

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  1. 14. Psychopharmacology for Pain Medicine 경희의료원 마취통증의학과 R2 전주연

  2. EPIDEMIOLOGY • Pain clinic population의 60~80%는 DSM criteria를 충족하는 psychiatric illness 갖는다. • Major depression (30~50%), anxiety disorder, personality disorders, somatoform disorders, and substance use disorders. • Major depression , anxiety disorders -M/C, medication에 best response • Psychiatric illness improvement 1) pain level의 감소 2) pain의 만성화에 대한 acceptance 향상 3) functionality 향상 4) 삶의 질 향상

  3. PSYCHIATRIC NOSOLOGY • DSM-Ⅳ, ICD-10 : Psychiatirc diagnosis를 위한 outline 를 제시, reliability가 높다. • 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.

  4. 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

  5. MAJOR DEPRESSION AND SUBTHRESHOLD DEPRESSION Symptom • Situational depression과 구별점 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 level의 변화.(적어도 2주이상 지속) • Beck’s 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.

  6. MAJOR DEPRESSION AND SUBTHRESHOLD DEPRESSION Treatment • 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.

  7. MAJOR DEPRESSION AND SUBTHRESHOLD DEPRESSION Treatment • 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 (15%:libido↓, impotence, ejeculatory disturbance, or anorganism) • Metabolism : Hepatic oxidation에 의해. Cytochorome P450 enz.을 induce and/or inhibit –간에서 대사된 다른 약들의 serum level변화시킨다. (carbamazepine, lithium, antipsychotics and a commonly used analgesics, methadone) • Discontiuation : Tapered down slowly to avoid a withdrawal syndrom.(Headache, nausea, diarrhea, or myalgia)

  8. MAJOR DEPRESSION AND SUBTHRESHOLD DEPRESSION Treatment • 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.

  9. MAJOR DEPRESSION AND SUBTHRESHOLD DEPRESSION Treatment • 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

  10. MAJOR DEPRESSION AND SUBTHRESHOLD DEPRESSION Treatment • 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 )

  11. MAJOR DEPRESSION AND SUBTHRESHOLD DEPRESSION Treatment • 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

  12. MAJOR DEPRESSION AND SUBTHRESHOLD DEPRESSION Treatment • 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 • Mechanism:serotonin-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.

  13. 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.

  14. ANXIETY DISORDER Treatment • Antidepressant • 2-4weeks to see improvement. • Dose 증가는 very slowly하게 행해져야 함. • 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.

  15. ANXIETY DISORDER Treatment • Benzodiazepines(BZDs) and Buspirone • Ix:Acute 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.

  16. 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 중요. Thyroid and kidney에 영향 : must be monitored. • Sparse analgesic effect

  17. 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 (적어도 2주에 한번씩 platelet check) sedation, dizziness, hepatitis.

  18. 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)

  19. 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

  20. 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)

  21. 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.

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