Amitriptyline scientific update |
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J Rheumatol. 2007 May;34(5):1125-32. Epub 2007 Apr 15.
Huber AM, Tomlinson GA, Koren G, Feldman BM.
From the Division of Pediatric Rheumatology, IWK Health Centre and Dalhousie University, Halifax, Nova Scotia.
Amitriptyline to Relieve Pain in Juvenile Idiopathic Arthritis: A Pilot Study Using Bayesian Metaanalysis of Multiple N-of-1 Clinical Trials.
OBJECTIVE: Using serial N-of-1 trials and subsequent analysis with Bayesian methods may allow study of therapies
using small numbers of subjects. Our research questions were: (1) Can serial N-of-1 trials analyzed with Bayesian
statistical techniques be used to estimate the population effect of a therapeutic intervention? (2) Compared to
placebo, how likely is it that low-dose amitriptyline therapy in children aged 10-18 years with active
polyarticular-course juvenile idiopathic arthritis (JIA) results in a significant improvement in pain? METHODS: Six
children (age 10.3-16.3 yrs, 4 girls) were enrolled. There were 3 pairs of randomized, double-blinded treatments
(amitriptyline 25 mg or placebo) per participant. Each treatment lasted 2 weeks, with a 1 week washout. The primary
outcome was pain, measured by 10 cm visual analog scale. Assessments were at the beginning and end of each
treatment. A Bayesian statistical model was used to determine the treatment effect. Values < 0 indicated
superiority of amitriptyline. RESULTS: Bayesian techniques were used successfully to obtain estimates of population
effect, despite the small number of participants. The mean treatment effect for pain was 0.67 (SD 0.89, 95%
credible interval -0.99, 2.55). The probability that the treatment effect was < 0 was only 16%. CONCLUSION: These
methods can be used successfully to estimate population effects when sample sizes are small. It is unlikely that
amitriptyline reduced pain by a clinically significant amount in these children with polyarticular JIA. These
methods may be particularly suited to pilot studies and the study of rare illnesses.
Anesth Analg. 2007 May;104(5):1256-64,
Punke MA, Friederich P.
Department of Anesthesiology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Amitriptyline is a potent blocker of human Kv1.1 and Kv7.2/7.3 channels.
BACKGROUND: Kv1.1 and Kv7.2/7.3 channels control excitability of neuronal cells. As hyperexcitability is a sign of
neuropathic pain, epilepsy, and anxiety disorders, these channels may be important molecular targets of
amitriptyline that cause pharmacological as well as toxicological effects by altering neuronal excitability. Since
the molecular mechanisms underlying these effects of amitriptyline have not been fully elucidated, we aimed to
characterize the interaction of amitriptyline with human Kv1.1 and Kv7.2/7.3 channels. We also intended to
establish the interaction of amitriptyline with the Kv7.2/7.3 channel opener, retigabine. METHODS: Kv1.1 and
Kv7.2/7.3 channels were expressed in human embryonic kidney cells and in Chinese hamster ovary cells. The effects
of amitriptyline and retigabine were studied with the patch-clamp technique. RESULTS: Amitriptyline inhibited Kv1.1
and Kv7.2/7.3 channels in a concentration-dependent and reversible manner. The IC50-value was 22 +/- 3 microM (n =
33) and 10 +/- 1 microM (n = 40), respectively. Deactivating inward currents of Kv7.2/7.3 channels were inhibited
with an IC50-value of 4.2 +/- 0.6 microM (n = 32). Inhibition of Kv7.2/7.3 channels by amitriptyline reversibly
depolarized the resting membrane potential. Retigabine reversed both the inhibitory action of amitriptyline on
Kv7.2/7.3 channels as well as the depolarization of the membrane potential. CONCLUSIONS: Since amitriptyline
inhibited Kv1.1 and Kv7.2/7.3 channels only at toxicologically relevant plasma concentrations, our results suggest
a role for these channels in the neuroexcitatory side effects of amitriptyline. As the inhibitory effects of
amitriptyline were reversed by retigabine, a combination of amitriptyline and retigabine could be of additional
benefit in the therapy of neuropathic pain.
Headache. 2007 Apr;47 Suppl 1:S52-7.
Ramadan NM.
Current trends in migraine prophylaxis.
A variety of drugs from diverse pharmacological classes are in use for migraine prevention. Traditionally, they
have been discovered by serendipity. Examples include beta-adrenergic blockers, anticonvulsants, tricyclic
antidepressants, and serotonin receptor antagonists. The mechanisms of action of migraine preventive drugs are
multiple but it is postulated that they converge on two targets: (1) inhibition of cortical excitation; (2)
restoring nociceptive dysmodulation. The antiepileptic drugs (e.g., topiramate, valproate, gabapentin), calcium
channel blockers such as verapamil, and inhibitors of cortical spreading depression are some examples of drugs that
reduce neuronal hyperexcitability. On the other hand, modulators of the serotonergic and adrenergic systems and
cholinergic enhancing drugs may restore descending nociceptive inhibition and play a role in migraine prevention.
To date, Level 1 evidence and clinical experience favor the use of the antidepressant amitriptyline, the
anticonvulsants divalproex and topiramate, and the beta-adrenergic blockers propranolol, timolol and metoprolol as
first line migraine preventive drugs. The evidence for others (e.g., verapamil) is not as strong. Migraine
preventive drugs have varying degrees of adverse effects, some of which could be limiting, and their efficacy
should balanced with their risks of adverse effects, patients' expectations and desires, and compliance. It is
hoped that future migraine preventive drugs target migraine mechanisms more specifically, which could well enhance
the therapeutic index.
J Low Genit Tract Dis. 2006 Oct;10(4):245-51.
Reed BD, Caron AM, Gorenflo DW, Haefner HK.
1Department of Family Medicine, University of Michigan, Ann Arbor, MI, 2University of Michigan Medical School, University of Michigan, Ann Arbor, MI, and 3Department of Obstetrics and Gynecology, University of Michigan, Ann Arbor, MI.
Treatment of vulvodynia with tricyclic antidepressants: efficacy and associated factors.
OBJECTIVE.: To determine the efficacy of tricyclic antidepressants (TCAs) as treatment for vulvodynia, and to identify demographic factors and pain characteristics associated with improvement. MATERIALS AND METHODS.: Between January 2001 and April 2004, women diagnosed with vulvodynia were offered TCA therapy. The patients rated their worst recent pain on a 10-point scale at baseline and at follow-up; improvement was classified as at least 50% reduction in reported pain from baseline. RESULTS.: Of 271 women diagnosed with vulvodynia, 209 (77.1%) were treated initially with a TCA (amitriptyline [n = 183], desipramine [n = 23], and other tricyclic medications [n = 3]). One hundred sixty-two (59.8%) of the women were followed up at a median period of 3.2 months after their initial visit, including 122 women who had started on a TCA. Of 83 women taking a TCA at the first follow-up, 49 (59.3%) improved by more than 50%, compared with 30 of 79 women not taking TCA at follow-up (improvement rate = 38.0%; p =.007; odds ratio = 2.35; 95% CI = 1.23-4.42). Multivariate analysis indicated that age, severity of pain, diagnosis (localized vs generalized vulvar pain), length of time with pain before treatment, age at menarche, use of oral contraceptives, and the number of previous pregnancies were not associated with the outcome; however, taking a TCA at the time of the first follow-up was strongly associated with improvement (p <.001; odds ratio = 4.23; 95% CI = 1.98-9.01). Repeated analysis including only those women prescribed with amitriptyline rather than any tricyclic revealed similar results. CONCLUSIONS.: Women with vulvodynia who were prescribed a TCA in general (or amitriptyline, specifically) were more likely to have pain improvement compared with those women not taking these medications at follow-up. Randomized, controlled studies of TCAs versus other treatments are needed to clarify the overall effectiveness of these drugs.
Drugs. 2005;65(7):927-47.
Wilson S, Argyropoulos S.
Psychopharmacology Unit, University of Bristol, Bristol, UK.
Antidepressants and sleep: a qualitative review of the literature.
Most antidepressants change sleep; in particular, they alter the physiological patterns of sleep stages recorded overnight with EEG and other physiological measures. These effects are greatest and most consistent on rapid eye movement (REM) sleep, and tend to be in the opposite direction to the sleep abnormalities found in major depression, but are usually of greater degree. Reductions in the amount of REM sleep and increases in REM sleep onset latency are seen after taking antidepressants, both in healthy volunteers and in depressed patients. Antidepressants that increase serotonin function by blocking reuptake or by inhibiting metabolism have the greatest effect on REM sleep. The decrease in amount of REM sleep appears to be greatest early in treatment, and gradually diminishes during long-term treatment, except after monoamine oxidase inhibitors when REM sleep is often absent for many months. Sleep initiation and maintenance are also affected by antidepressants, but the effects are much less consistent between drugs. Some antidepressants such as clomipramine and the selective serotonin receptor inhibitors (SSRIs), particularly fluoxetine, are sleep-disturbing early in treatment and some others such as amitriptyline and the newer serotonin 5-HT2-receptor antagonists are sleep promoting. However, these effects are fairly short-lived and there are very few significant differences between drugs after a few weeks of treatment. In general, the objectively measured sleep of depressed patients improves during 3-4 weeks of effective antidepressant treatment with most agents, as does their subjective impression of their sleep. Sleep improvement earlier in treatment may be an important clinical goal in some patients, perhaps when insomnia is particularly distressing, or to ensure compliance. In these patients, the choice of a safely used and effective antidepressant which improves sleep in short term is indicated. Patients with other sleep disorders such as restless legs syndrome and REM sleep behaviour disorder should be identified before choosing a treatment, as some antidepressants worsen these conditions. Conversely, there is evidence that some antidepressants may be useful in the treatment of sleep disorders such as night terrors.
N Y State Dent J. 2005 Jun-Jul;71(4):38-42.
Guler N, Durmus E, Tuncer S.
Yeditepe University, Faculty of Dentistry, Department of Oral and Maxillofacial Surgery, Istanbul, Turkey.
Long-term follow-up of patients with atypical facial pain treated with amitriptyline.
OBJECTIVE: The aim of this study was to assess the efficacy of low-dose amitriptyline in patients with atypical facial pain for one-year follow-ups. PATIENTS AND METHODS: Sixteen patients, ten females and six males, ranging in age from 15 to 77 years (mean 46.6 +/- 15.95 years), participated in the study. The onset, duration and temporal pattern of pain, events related to pain, drugs used before treatment and side effects of amitriptyline were recorded. The severity of pain was evaluated by using the visual analogue scale (VAS). Patients were followed for up to 12 months. RESULTS: The results showed that the onset of pain was related to dental pain in half of patients; and 10 patients had continuous pain. The mean VAS scores for pretreatment, post treatment, and 1, 3, 6, and 12 months were 9.6, 4.8, 2, 0.8, 0.3 respectively. In 12 patients, pain was reduced at the first month (p<0.05). All patients, except one, were pain-free at 12 months. It was statistically significant in achieving pain relief for 12 months (p<0.05). The common side effects of the drug were dry mouth and drowsiness. CONCLUSION: Data obtained from this study suggested that amitriptyline may be preferred in patients with atypical facial pain for rapid, satisfying analgesic effects. Long-term follow-up should be conducted to determine the analgesic effects and to prevent recurrence, even if the analgesic effect occurs in a short time.
Clin J Pain. 2005 Jul-Aug;21(4):364-9.
Altier N, Dion D, Boulanger A, Choiniere M.
Centre des Grands Brules, Hotel-Dieu du Centre Hospitalier de l'Universite de Montreal, Montreal, Quebec, Canada.
Management of chronic neuropathic pain with methadone: a review of 13 cases.
The synthetic opioid methadone has generated much interest in recent years among clinicians involved in the management of intractable chronic cancer pain. Its use as an analgesic is starting to extend to the treatment of noncancer pain, particularly neuropathic pain. Unfortunately, the evidence for its use in the management of neuropathic pain is limited to a few case studies. We examined retrospectively during a 12-month study period the clinical response of all 13 patients at our pain clinic who were prescribed methadone in an attempt to control neuropathic pain resistant to conventional analgesics. A questionnaire was also administered to the 9 patients who continued to take methadone at 12 months posttreatment. A total of 4 patients (31%) discontinued it by the end of the 12-month study period. Patients discontinued methadone due to the absence of pain relief and due to various intractable, undesirable side effects. Somnolence was the most common adverse effect reported, followed by nausea, constipation, and vomiting. All patients took coanalgesics (eg, amitriptyline, gabapentin) or other analgesics (eg, morphine, nonsteroidal anti-inflammatory drugs) during methadone treatment to control pain. The 9 patients who continued to take methadone at 12 months reported experiencing on average 43% pain relief (range 0-80%), 47% improvement in quality of life (range 0-100%), and 30% improvement in quality of sleep (range 0-60%). Methadone was effective at relieving pain and ameliorating quality of life and sleep in 62% of patients. These findings suggest that methadone can offer an acceptable success rate for the treatment of neuropathic pain. Prospective randomized, placebo-controlled studies are now needed to examine more rigorously the benefits of methadone for this type of pain.
Amitriptyline description...
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Drug category:Antidepressants
 Amitriptyline scientific update
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