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14.Psychopharmacology for Pain Medicine

14.Psychopharmacology for Pain Medicine. R3 김형준. EPIDEMIOLOGY. Pain clinic population 의 60~80% 는 psychiatric illness 갖는다 Major depression (30~50%), anxiety disorder, personality disorders, somatoform disorders, substance use disorders Major depression , anxiety disorders

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14.Psychopharmacology for Pain Medicine

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  1. 14.Psychopharmacology for Pain Medicine R3 김형준

  2. EPIDEMIOLOGY • Pain clinic population의 60~80%는 psychiatric illness 갖는다 • Major depression (30~50%), anxiety disorder, personality disorders, somatoform disorders, substance use disorders • Major depression , anxiety disorders -> m/c , medication에 가장 잘 반응함 • Psychiatric illness improvement -> 1) diminished pain level 2) greater acceptance of the chronicity of pain 3) improved functionality 4) improved quality of life

  3. MAJOR DEPRESSION AND SUBTHRESHOLD DEPRESSION A. Symptoms • Major depression이 Situational depression과 구별되는 점 1) Persistently low mood 2) Self attitude change 3) Change in vital sense - 적어도 2주 이상 지속 • Beck’s triad - hopless, hapless, and helpless • Suicidal thought - depressive symptom의 severity를 반영함 • Major depression은 persistent pain의 serious complication이며,효과적으로 치료되지 않는다면 모든 통증 치료의 효과를 감소시킬 수 있음

  4. MAJOR DEPRESSION AND SUBTHRESHOLD DEPRESSION B. 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 • 약제의 선택과 관계없이, 환자의 대략 60%가 initial antidepressant 처방에 반응함 (적어도 50%의 향상을 보임) • Major depression을 가진 pain 환자는 치료에 대한 증가된 resistance (특히 pain이 효과적으로 manage되지 않았을 때)

  5. MAJOR DEPRESSION AND SUBTHRESHOLD DEPRESSION B. Treatment 1) Selective serotonin reuptake inhibitors (SSRIs) • Blockade of the presynaptic serotonin reuptake pump in the CNS • Antidepressant efficacy + low side effect -> the most widely prescribed • Few independent pain properties • No absolute contraindications except in patients on MAOIs

  6. MAJOR DEPRESSION AND SUBTHRESHOLD DEPRESSION B. Treatment 1) Selective serotonin reuptake inhibitors (SSRIs) • Side effect - nausea, diarrhea, tremor, and headache sedation, overstimulation sexual side effect (15%) • Hepatic oxidation에 의해 대사되며 간에서 대사되는 다른 약들의 serum level을 변화시킴 • Cytochorome P450 enz을 induce and/or inhibit - 주로 TCAs와 benzodiazepines의 level을 증가시키고 carbamazepine, lithium, antipsychotics , a commonly used analgesics, methadone 등에 영향을 줌

  7. MAJOR DEPRESSION AND SUBTHRESHOLD DEPRESSION B. Treatment 2) Tricyclic antidepressants (TCAs) • Oldest classes of andtidepressants • Inhibiting both serotonergic and noradrenergic reuptake • Analgesic properties Diabetic neuropathy pain, chronic regional pain syndrome, chronic headache, poststroke pain, and radiculopathy • Side effect - anticholinergic and antihistamine effect, decreased seizure threshold, Quinidine like properties (proarrythmic, prolong the QTC interval)

  8. MAJOR DEPRESSION AND SUBTHRESHOLD DEPRESSION B. Treatment 2) Tricyclic antidepressants (TCAs) • Strongly protein-bound + undergo first-pass hepatic metabolism • Hepatic clearance는 P450 enz과 관련됨 SSRI, cimetidine, methylphenidate -> TCA plasma level을 증가 phenobarbital, carbamazepine, cigarette smoking -> TCA plasma level을 감소 • Analgesic effect dose 25-50mg Antidepressant effect dose 75-150mg • Abrupt discontinuation 후에 withdrawal Sx 발생할 수 있음 - fever, sweating, headache, nausea, dizziness

  9. MAJOR DEPRESSION AND SUBTHRESHOLD DEPRESSION B. Treatment 3) Serotonin-Norepinephrine reuptake inhibitors (SNRIs) • TCAs와 마찬가지로 Inhibiting serotonin and norepinephrine reuptake • No alpha-1, cholinergic, or histamine inhibition • Superior analgesic properties of TCAs (NMDA antagonism and sodium channel blockade) • Side effect - nausea, somnolence, dry mouth, dizziness, nervousness, constipation, anorexia, or sexual dysfunction. • 150mg/day 이상의 용량에서 SBP를 10mmHg 이상 증가시킬 수 있음 (norepinephrine reuptake inhibition)

  10. MAJOR DEPRESSION AND SUBTHRESHOLD DEPRESSION B. Treatment 4) Other Antidepressants 1. Buproprion • Noradrenergic and dopaminergic reuptake pump inhibitor • Significant psychostimulant properties - depression, ADHD, smoking cessation • Independent analgesic effects - neuropathic condition, effective in alleviating the sedative effects of opioid. • Side effect - seizure (450-600 mg/day), nervousness, headache, irritability, and insomnia

  11. MAJOR DEPRESSION AND SUBTHRESHOLD DEPRESSION B. Treatment 3) Other Antidepressants 2. Mirtazapine • Antagonism of serotonin and central presynaptic alpha2-adrenergic receptor, stimulating serotonin and norepinephrine release • Side effect - weight gain, agranulocytosis and neutropenia. 3. Trazodone and Nefazodone • Serotonin-2 antagonist/reuptake inhibitors • Major depression and insomnia • Side effect - priapism, sedation, dizziness, dry mouth, orthostatic hypotension, constipation, and headache

  12. ANXIETY DISORDERS A. Symptoms • Anxiety disorder는 generalized anxiety (m/c), panic disorder, OCD, PTSD를 포함 • Anxiety는 biological component를 갖고 있기 때문에 medication에 잘 반응함 1. Pathological anxiety Interfere normal funtioning (restless, fatigued, irritable, and poor concentration) 2. Trait anxiety Excessive worry and concern about routine matter Great difficulty controlling worry 3. Situational anxiety in pain patients Anxiety about pain and its negative consequences Anxiety amplifies pain perception and pain complaints

  13. ANXIETY DISORDERS B. Symptoms 1) Antidepressant • 환자에서 원하는 improvement를 보기 위해서는 2-4 주 걸림 • Compliance를 향상시키기 위해서 anxiety 환자들은 side effects를 잘 견디지 못하기 때문에 용량 증가를 매우 천천히 시행해야 함 • Anxiety의 overall level를 감소시키고 anxiety나 panic attacks을 예방하는 데 효과적 하지만 acute anxiety의 치료에는 효과 없음 • SSRI – antidepressant 중에서 가장 효과적임 • TCAs – OCD에 유용 • Mirtazapine • Buproprion - anxious feature를 가진 depression의 치료에 효과적 • SNRIs - generalized anxiety에 효과적

  14. ANXIETY DISORDERS B. Symptoms 2) Benzodiazepines (BZDs) and Buspirone • Acute anxiety, panic attack, generalized anxiety에 유용 1. Benzodiazepines (BZDs) • Acute anxiety이나 panic attacks은 Short acting BZD로 치료할 수 있음 (Lorazepam – rapid onset, half-life of 10 to 20 hours) • Side effects - profound sedation, confusion, respiratory depression • Fatal in overdose, addictional potential 2. Buspirone • Effective acute anxiolytic, no addictive properties • Psychomotor나 cognitive fx을 손상시키지 않음 • Side effects – headache, dizziness, fatigue, paresthesia, GI upset

  15. MOOD STABILIZERS • Antimanic and antidepressant properties • Bipolar disorder에서 가장 흔히 처방되는 medication 1) Lithium • Major depressive disorder의 치료에 antidpressants와 사용되어 효과를 증대시킴 • Chronic daily headaches과 cluster headaches의 예방에 사용됨 • Narrow therapeutic range - serum level 중요하고 thyroid와 kidney에 영향를 주기 때문에 반드시 monitor해야 함 • Analgesic effect의 거의 없음

  16. MOOD STABILIZERS 2) Valproic acid • Duration of action : 8-12hr. • Antimanic and antidepressant effects Migraine prophylaxis와 seizure treatment에 사용됨 • Therapeutic and toxicity range - serum level monitored 치료시작 전에 CBC와 LFT를 check해야 함 • Side effects - thrombocytopenia (2주에 한번씩 platelet check) sedation, dizziness, hepatitis

  17. NEUROLEPTICS • Also termed antipsychotics • Schizophrenia와 depression, mania, delirium 등의 psychotic • symptom에서 사용 • Independent pain properties • Serious side effects – Parkinsonism, tardive dyskinesia (pain medicine에서 사용이 제한됨) 1) Typical neuroleptics (Haloperidol) • Antagonism of dopamine receptors (특히 D2 receptor) 2) Atypical neuroleptics (Clozapine) • Lesser degree of D2 receptor antagonism, greater degree of D4 receptor antagonism, some degree of serotonin-2 receptor blocking –> Extrapyramidal, anticholinergic, cardiac side effects가 적음 • 당뇨환자에서 사용할 경우 glucose tolerance를 줄여 serum glucose level을 증가시킬 수 있음

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