Slow Titration Schedule Research Articles

Non-opioid analgesics: other: Intrathecal ziconotide (Prialt™T) relieves idiopathic peripheral neuropathic pain: A case report

Patient CJM, a 40-year-old man, was referred for treatment of burning pain in his lower extremities. His diagnosis by exclusion was idiopathic peripheral neuropathy. On presentation to the pain clinic in 1997, CJM described burning pain in a stocking distribution over both feet to his ankles. He also described intermittent swelling, but physical exam revealed no sympathetic changes. Conventional pain therapy provided only mild relief. Lumbar sympathetic blockade provided no benefit. A 7-day spinal cord stimulation trial was quite successful; the patient reported adequate analgesia but no reduction in medication usage. Unfortunately, due to lead migration, the generator had to be explanted. Intraspinal opioids provided substantial relief but were associated with problematic edema. An intraspinal opioid rotation was performed, placing the patient on hydromorphone. When the patient was reexamined on July 11, 2002, he had significant edema of the lower extremities causing 2+ pitting and skin fissures. His overall body habitus had changed with weight gain of over 150 lbs. Intraspinal opioids were slowly weaned to prepare for ziconotide infusion, a new non-opioid N-type calcium channel blocker. Ziconotide was initiated on December 11, 2002 at 2.4 mcg/d increased to 2.6 mcg/d using a slow titration schedule. The patient reported decreased sleep and increased energy; his analgesia was profound compared with his earlier modalities. Another dosage escalation was associated with mild sedation. The patient asked for another escalation and the infusion was increased to 6.0 mcg/d. As well as excellent pain relief, CJM reported some side effects, including word-finding difficulty, sleeplessness, dry mouth, mild agitation, and nystagmus. These events resolved with dosage reduction. CJM has remained at 3.1 mcg/d since September 17, 2003 with no recurrence of adverse effects. Medication regimen was simplified to oxycodone CR 20 mg BID with adjunctive bupropion. Ziconotide was effective with a purely neuropathic pain disorder.

Pharmacological treatment of psychotic agitation.

The presentation of agitated psychotic patients to psychiatric emergency services is a common occurrence. The traditionally accepted treatment for such patients involves the use of a typical antipsychotic, generally haloperidol. More recently benzodiazepines, such as lorazepam, have been used in combination with antipsychotics due to their sedative properties and relatively benign adverse effect profiles. Standard clinical protocol at many institutions involves the intramuscular administration of 5 to 10mg of haloperidol and 1 to 2mg of lorazepam. Atypical antipsychotics have gained acceptance as first-line treatments for psychotic disorders. These drugs are seen as an improvement over traditional antipsychotics because of their increased efficacy and reduced extrapyramidal effects. The utility of atypical antipsychotics in the emergency setting has been relatively unexplored because slow titration schedules or dose-limiting adverse effects for some members of the class have made this form of treatment impractical. However, the recent availability of oral liquid and rapidly dissolving tablet preparations of some atypical agents has provided useful alternatives in some cases. Nevertheless, for many patients a parenteral drug is the only desirable or feasible treatment option. Intramuscular preparations of the atypical antipsychotics olanzapine and ziprasidone have been developed, and are close to launch in the US. The availability of a rapid-acting intramuscular preparation of an atypical antipsychotic could represent a significant advancement in the treatment of agitation associated with psychosis.

Carbamazepine in comparative trials: pharmacokinetic characteristics too often forgotten.

To compare the use of carbamazepine (CBZ) in comparative monotherapy trials with its use in practice. CBZ is often the drug of first choice for partial onset seizures and is frequently used as the reference drug in comparative trials with newly developed antiepileptic compounds. There are several issues related to CBZ that may have an impact on the final outcome of these trials. CBZ has nonlinear time-dependent kinetics due to autoinduction, and this may cause adverse reactions on starting treatment; somnolence and rash usually occur in the first weeks and may be related to the dose and titration schedule. Total daily dose or the serum levels of the drug do not correlate with therapeutic efficacy. Review of the current literature on the pharmacokinetics properties of CBZ and of comparative trials of new antiepileptic drugs that used CBZ as the reference drug. The use of CBZ differed in comparative clinical trials and in clinical practice, with slower and lower titration rates used in the latter. This may be disadvantageous for CBZ because its pharmacokinetics peculiarities are ignored. If CBZ is to be used in these trials, titration rates and dosages should resemble those used in clinical practice because this is likely to improve efficacy and tolerability. Otherwise, the results of these trials may support regulatory applications but have little relevance to clinical practice. We suggest an initial CBZ dose of 100 mg/d and a slow titration schedule with dose incremental steps of 100 mg/d every week up to 600 mg/d. Blood levels should determine the initial target dose, but after this has been achieved titration should be based on seizure control and tolerability rather than by blood levels.