MOOD STABILIZERS & ADJUNCT AGENTS © www.RxFiles.ca Brent Jensen BSP Jun 13 Generic/Form SIDE EFFECTS MONITOR COMMENTS/ DRUG INTERACTIONS INITIAL & USUAL DOSE $ TRADE g=generic avail. Q6-12 Months DRUG LEVEL MAX DOSE RANGE /100day Common: GI N/V, drowsy, dizzy, unsteady, CBC,Platelets, √ BPAD -acute mania, rapid cycle, ↑ Carbamazepine level by: 200mg po bid 24 Carbamazepine(CBZ) cimetidine, clarithro/erythromycin, danazol, 200mg hs pruritic rash<10% may cross react with phenytoin & phenobarb; TSH,LFT, mixed & prophylaxis TEGRETOL g diltiazem, felodipine,fluoxetine, fluvoxamine, 200mg CR bid 36 dose related GI/CNS ς ς ↓WBC . CR tab: less SE . grapefruit juice, isoniazid, ketoconazole, 1800mg/day Lytes, √ trigeminal neuralgia, seizures (100 ,200 mg chew tab) 200mg po tid 33 ς ς lamotrigine, metronidazole, nefazodone, Rare: aplastic anemia, ↑ liver enzymes, Level Option for aggressive patients & (autoinduction of (200 ,400 mg CRtab) phenobarbital, propoxyphene, ritonavir,verapamil 400mg po bid 42 (200ς mg tab) heart abnormalities, ↓ serum sodium/Vit K, those with neurologic dx. & valproate P450 system complete in 4 weeks; 400mg CR bid 64 ( susp) P1,P2‐3 L / porphyria ↓ Carbamazepine level by: 20mg/ml SLE, exfoliative dermatitis, ocular effects, ECG for pts CI: hepatic dx; safe in renal dx may start low-dose & Pregnancy category→ Malformation <5% 2% phenytoin,phenobarb,St.Johns 600mg po hs 33 ? cleft palate, spina bifida OR=2.6, but ↓WBC (persistent ), ↓ T3/T4, alopecia, >45yrs 17-54 umol/l wort,theophylline ↑ weekly x4 weeks; HLA-B* 1502 HLA-A* 3101 baseline 1:1000. ↑↑ with DVA. Asian & ; Caucasian & : ↑↑risk skin rx. Wait until after auto-induction phase (4wks)! Carbamazepine ↓ levels of: Valproate also ↓’s SE. Wait 800mg po hs 42 Folic acid 5mg/d 3mo prior & 1st trimester, ~ 4 wks for levels.) then 0.4-1mg/day. WEIGHT GAIN = minimal Less DI with oxcarbazepine than CBZ INDUCES P450 3A4 System^ Divalproex Common: nausea, diarrhea, dizzy, ataxia, CBC,Platelets, √ BPAD acute mania,rapid cycle, ↑ Valproic acid level by: 250mg od 250mg po bid 45 somnolence, sedation, tremor, fatigue, LFT mixed, prophylaxis & depression aspirin, cimetidine, erythromycin, felbamate, (DVA) P L fluoxetine, isoniazid, salicylates 250mg po tid 64 confusion, headache, abdominal cramps, Level √ seizures & migraine prophylaxis; EPIVAL g ↓ Valproic acid level by: 500mg po bid 83 hair loss often reversible, menstrual disturbances Option for aggression; 3000mg/day (125,250,500mg EC tab); carbamazepine, cholestryramine, lamotrigine, 1gm po hs 83 Rare: ↓platelets & WBC, hepatotoxic, Pregnancy registry : heart defect & Safe in renal dx. meropenem,phenobarbital,phenytoin,rifampin,ritonavir χ⊗ 2C9 500mg po tid 120 1000mg/10 ml vial ) skin rx's,pancreatitis,neural tube defects 1-2% spina bifida 10.7 vs 2.9% in control gp. Valproic acid ↑ levels of: Acute Mania -Oral load of epoxide ↑malformations with valproate Artama 05. amitriptyline, carbamazepine (ie.↑ SE), Caution: polycystic ovaries Perucca 05 20mg/kg has been used Mainly an enzyme inhibitor -prodrug of VPA; esp >1g/d Folic acid 5mg/d clonazepam, diazepam,ethosuximide,lamotrigine, WEIGHT GAIN= ++ (up to 59%, st see valproic acid below 3mo prior & 1 trimester, then 0.4-1mg/day. CI: hepatic dx & kids≤2yr lorazepam, phenobarbital, TCAs, warfarin st trimester. more common in ; mean ↑ of 8-14kg) May ↓IQ in newborn. Concern 1 400-700 umol/l Not ↓ effect of BCP's Lamotrigine Common: dizzy, nausea, vomiting, CBC,LFT √ seizures; Option: Alt./adjunct for ↑ Lamotrigine level by: 25mg hs 50mg po bid 65 asthenia, headache, somnolence, ataxia, ↑ BPAD I for acute depression & sertraline, valproate 100mg po bid 122 LAMICTAL g (25ς,100ς,150ς mg tab; alertness, diplopia, abdominal pain, rash Bipolar II for rapid cycling FDA Jun03 ↓ Lamotrigine level by: BCP's, ↑ only 25- 150mg po bid 177 ς P L #, 1st 2months, <0.1% # 5 mg chewable tab) Rare:Stevens-Johnson Sx Rash 10% → life threatening 0.3% carbamazepine, phenytoin, 50mg/week If using with valproate: W (If drug related/severe, D/C at first sign of rash) phenobarb, primidone, rifampin, ritonavir ↑ (2mg chewable tab ) 12.5mg/wk & toxic epidermal necrolysis, hepatotoxic, increments 25mg hs start 22 Not teratogenic in animal, but ↑ risk leukopenia, aseptic meningitis & tics in kids 4-39umol/l (? Sig/not routinely avail.) NO EFFECT on P450 enzymes of fetal death. ↑ non-syndromic oral 100mg po hs 65 Breast feeding: caution b/c of rash cleft. Pregnancy: ↓level & ↑level in WEIGHT GAIN= neutral effect Rarely ↓ effect of BCP's & folic acid Mono Therapy dose 50-400mg/d; breast milk. ↑↑ risk if with DVA. 400mg/day 50-200mg/d with divalproex FDA ≥12yr Lithium carbonate Common: nausea/vomiting/diarrhea, edema, CBC,TSH, √ BPAD : acute mania & ↑ Lithium level by: 300mg hs 300mg po hs 27 ECG ACE inhibitors, ARBs,carbamazepine, polyuria, polydypsia, , ↑WBC, alopecia, prophylaxis, mild depression 300mg po bid 31 CARBOLITHg,, Ca channel blockers, diuretics, DURALITH acne, psoriasis, hypothyroidism, Urinalysis, Suicide reduction for BPAD pts ⊗ P1,P2‐3 L not 300mg SR bid 76 ++ fluoxetine, metronidazole, NSAIDS 1800mg/day (150,300,600mg cap; Lytes, Ca ASA hyperparathyroidism, monitor for toxicity, ↑ Option:Cluster headache, OCD, , sodium depletion, spironolactone, 600mg po hs 37 LITHMAX ⊗ ++ + ↓ propranolol or Lithium dose helps SCr, Level antidepressant augmentation & aggression Maintain consistant 300mg SR tab ) Ca , ↑ K & tremor ↓ Lithium level by: caffeine, 8-12hr Safe to use in liver dx salt (Na+) diet! 300mg po tid 36 Ebstein’s Trough : PMS-LITHIUM Level 1.5-2mmol/l:drowsy,ataxia, slurred metamucil, NaCl, theophylline, ⊗ anomaly 0.1% caution 300mg SR tid 104 dose related,Tx Inderal CI: ↓renal fx, breast feeding topiramate Fetal echo at speech, hypertonicity, tremor ~0.8-1.1mmol/L CITRATE 900mg po hs 36 ~18 wks gest. Acute Mania 0.8-1.2 mmol/l Lithium↑ toxic by ↑ serotonin effect: Level >2mmol/l: arrhythmias, ↓ heart (in elderly χW l-tryptophan, MAOI's, sibutramine, verapamil 1200mg po hs 40 (300mg/5ml syrup ) rate, myocarditis, seizures, coma & death. 0.4-0.7 mmol/L) Maintenance Tx 0.6-1.0 mmol/l (Li+DVA or Li) >DVA Balance BPAD I relapse prevention With Antipsychotics- ↑ neurotoxicity WEIGHT GAIN= + (25-60% -mean gain 7.5kg) As per divalproex above As per divalproex above Valproic acid -VPA 250mg od 250mg po bid 47 Divalproex & valproic acid are not Pregnancy registry: heart defect & spina bifida g CBC,Platelets, 500mg po bid 121 DEPAKENE P L interchangeable medications (250mg cap; 500mg EC Depakene generally has more GI LFT 10.7vs2.9% in control gp. ↑ malformations with valproate 1gm po hs 121 Artama 05, esp >1g/d Perucca 05. Folic acid 5mg/d 3mo prior & 1st 3000mg/day Level cap; 250mg/5ml syrup) side effects than Epival As per divalproex above trimester, then 0.4-1mg/day. May ↓ IQ in newborns. 500mg po tid 179 Gabapentin Common: somnolence, dizzy, ataxia, NA √seizures; Option:Neuropathic pain Antacids ↓ by 20% absorption 100mg hs 100mg po bid 39 nystagmus, n/v, blurred vision, tremor, &Anxiolytic in severe Panic dx & NEURONTIN g NO other signif. interactions (↑ 100- 300mg po bid 83 P L slurred speech, rash, behavioral changes in little effect as 400mg/day (100,300,400 cap) social phobia,↓ dose if ↓ renal fx, With doses >600mg less is absorbed 400mg po bid 100 mood stabilizer increments) (600ς,800ςmg tab W ↑cost) kids & ↓WBC. WEIGHT GAIN= + (appears 3-25umol/l (? Significance/avail.) since mechanism is saturated 300mg po tid 124 dose related), euphoria; ?akathisia on withdrawal 3600mg/day Topiramate Common: nausea, dizzy, tremor, ataxia, CNS SE Weight loss ~4kg ?dose related ↓ Topiramate level by: 25mg hs 25mg po bid 103/283 carbamazepine & phenytoin (40%), TOPAMAX g somnolence, cognitive dysfunction, synergize with May minimize weight gain induced 50mg po bid 220/538 valproate (15%) ↑ only by (25,50,100,200mg tab; P L headache, paresthesias, sedation, fatigue, agents such as by other psychotropics 100mg po bid 190/512 diarrhea, metabolic acidosis, divalproex √ seizures; 80% Renal elimination ↑ toxicity of topiramate with: 25-50mg/week 15, 25mg sprinkle cap) Ketogenic diet; Aceta-,dor-& metho-zolamide 200mg po bid 275/751 nephrolithiasis & glaucoma acute angle, stop Tx! √ migraine prophylaxis (topiramate has carbonic anhydrase inhib. properties) increments 275/751 400mg po hs Hypospadias in male WEIGHT GAIN= loss possible + dva→ ↓ platelet&↑ encephalopathy Topiramate >200mg/d ↓ effectiveness : generic/Trade infants. Cleft lip/palate. 250-400mg/day Caution: ↓ sweating (seems dose & duration dependent & > in ) Renal stones1.5% thus try to ↑ fluid intake BCPs birth control pills especially in children =↓ dose for renal dysfx ς=scored =Exception Drug Status Sask χ =Non formulary in Sk Wcovered NIHB CI=contraindication CR=control release Dx =disease EC=enteric coated SE=side effect SR=sustained release ^ Carbamazepine ↓ level of: alprazolam, aripiprazole, bupropion, clonazepam, cyclosporine, dexamethasone, diazepam, doxycycline, ethosuximide, felodipine, fentanyl, irinotecan, lamotrigine, haloperidol, nefazodone, nevirapine, OC’S, phenytoin, phenobarbital, phenothiazines, pregnancy tests, risperidone, steroids, theophylline, triazolam, tricyclics, valproate, voriconazole & warfarin. Pregnancy: Most have teratogenic risk, risk > if multiple meds; try for monotherapy &↓serum level. Try to avoid in 1st trimester. Consider antipsychotic, benzodiazepine, ECT or ?lithium. Initiate folate 5mg/d, 3mo pre-conception, & 1st trimester, then 1mg/d. # eg. haloperidol, olanzapineW, quetiapine, risperidone,