Is SAPHO syndrome a target for antibiotic therapy?
Stellate ganglion blocks have been shown to provide effective pain relief in a number of different conditions involving the upper body. This was demonstrated in a 65-year-old woman who had experienced severe debilitating pain in her left temporomandibular joint (TMJ) and the surrounding area of her face for over 10 years. The pain was unresponsive to indomethacin, carbamazepine, sodium valproate, gabapentin, lithium, melatonin and amitriptyline. She had also had four surgical procedures to the TMJ without success. The pain was partially responsive to Syndol tablets and pregabalin, although the use of pregabalin was limited by its adverse effects. The patient underwent 13 ultrasound guided stellate ganglion blocks over a 24-month period which demonstrated 90% pain relief for up to 10 weeks. Pulsed radio frequency lesioning showed no benefit over stellate ganglion block. More recently, tapentadol was found to be effective and this replaced the stellate ganglion blocks.
The multi-drug resistance gene ABCB1 (or MDR1) encodes a P-glycoprotein (P-gp) that regulates passage of many substances across the blood-brain barrier. The antidepressant amitriptyline and its metabolites (including nortriptyline) are substrates for P-gp, and in mice lacking P-gp, penetration of amitriptyline, but not fluoxetine, into the brain is enhanced. We reasoned that polymorphic variation of P-gp may contribute to differing responses of patients to antidepressant drugs. A single nucleotide polymorphism (SNP) of ABCB1 (3435C>T) was recently correlated with expression levels and in vivo function of P-gp. We examined this SNP in patients with major depression enrolled in a randomized antidepressant treatment trial of nortriptyline and fluoxetine, and observed a significant association between nortriptyline-induced postural hypotension and 3435C>T (chi(2) = 6.78, df = 2, P = 0.034). Our results suggest that homozygosity for 3435T alleles of ABCB1 is a risk factor for occurrence of nortriptyline-induced postural hypotension (OR = 1.37, P = 0.042, 95% CI 1.01-1.86).
In a double-blind randomized controlled trial in an animal lab, intrathecal injection of drugs was performed in 30 Wistar male rats. We divided the subjects into 3 groups: group 1: 90 µL Doxepine (50 mM), group 2: 90 µl amitriptyline (60 mM). and group 3: 90 µL bupivacaine (23 mM). Then sensory, motor, and proprioceptive changes were measured at 1, 2, 3, 4, 6, and 12 hours by one examiner.
1. The block of K+ currents by amitriptyline and the related tricyclic compounds cyproheptadine and dizocilpine was studied in dissociated rat sympathetic neurones by whole-cell voltage-clamp recording. 2. Cyproheptadine (30 microM) inhibited the delayed-rectifier current (Kv) by 92% and the transient current (KA) by 43%. For inhibition of Kv, cyproheptaidine had a KD of 2.2 microM. Dizocilpine (30 microM) inhibited Kv by 26% and KA by 22%. The stereoisomers of dizocilpine were equally potent at blocking Kv and KA. 3. Amitriptyline, a weak base, was significantly more effective in blocking Kv at pH 9.4 (KD = 0.46 microM) where the ratio of charged to uncharged drug was 50:50 compared with pH 7.4 (KD = 11.9 microM) where the ratio was 99:1. 4. N-methylamitriptyline (10 microM), the permanently charged analogue of amitriptyline, inhibited Kv by only 2% whereas in the same cells amitriptyline (10 microM) inhibited Kv by 36%. 5. Neither amitriptyline nor N-methylamitriptyline had a detectable effect on Kv when added to the intracellular solution. 6. It is concluded that the uncharged form of amitriptyline is approximately one hundred times more potent in blocking Kv than the charged form. However, this does not seem to be due to uncharged amitriptyline having better access to an intracellular binding site.
MEDLINE (1966 to 2008), EMBASE (1974 to 2008), the Cochrane Collaboration Depression, Anxiety and Neurosis Controlled Trials Register and the Cochrane Central Register of Controlled Trials up to July 2008. No language restriction was applied. Reference lists of relevant papers and previous systematic reviews were hand-searched. Pharmaceutical companies and experts in this field were contacted for supplemental data.
Two authors decided which trials fitted the inclusion criteria and graded methodological quality independently.
Twenty five patients of endogenous depression fulfilling Feighner's criteria were selected for this study. It was found that the patients who improved with methylamphetamine responded to imipramine and those who did not improve with methylamphetamine improved with amitriptyline.
All randomised trials of tricyclic and related drugs for nocturnal enuresis in children were included in the review. Trials were eligible for inclusion if: children were randomised to receive tricyclics compared with placebo, other drugs or other conservative interventions for nocturnal bedwetting; participants with organic causes for their bedwetting were excluded; and baseline assessments of the level of bedwetting were provided. Trials focused solely on daytime wetting were excluded.