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PubMed1996

Comparative electrophysiological effects of the antidepressants fluvoxamine and amitriptyline in the canine heart after myocardial infarction.

We studied the effects of fluvoxamine and amitriptyline on epicardial activation delay of premature excitations, the effective refractory period, and the incidence of ventricular arrhythmias by programmed electrical ventricular stimulation in the canine heart after myocardial infarction. Additionally, we investigated whether the inhibition of norepinephrine reuptake by amitriptyline contributes to epicardial activation delay or arrhythmias by combination with propranolol pretreatment. Amitriptyline, at a dose of 3 mg/kg, significantly prolonged epicardial activation delay of premature excitations in the infarcted zone in a frequency-dependent manner (n = 10). Amitriptyline also prolonged epicardial activation delay of premature excitations in the normal zone (n = 10). The effective refractory period in the infarcted zone was significantly prolonged by amitriptyline at a dose of 3 mg/kg (n = 8). Amitriptyline increased the incidence of ventricular arrhythmias induced by programmed electrical ventricular stimulation (n = 8). Propranolol did not affect the epicardial activation delay caused by amitriptyline or the incidence of ventricular arrhythmias induced by programmed electrical ventricular stimulation (n = 6). Fluvoxamine, on the other hand, had no significant effect on epicardial activation delay of premature excitations (n = 10) or the effective refractory period (n = 8) in both the infarcted and normal zones. Fluvoxamine did not increase the incidence of ventricular arrhythmias induced by programmed electrical ventricular stimulation (n = 8).

Amitriptyline↗
PubMed1989

Controlled comparison of two doses of milnacipran (F 2207) and amitriptyline in major depressive inpatients.

A multicenter study compared the antidepressant efficacy and the tolerance of two doses of milnacipran (50 mg and 100 mg/day) and amitriptyline (150 mg/day) in three parallel groups of 45 major depressive inpatients defined by Research Diagnostic Criteria. After a wash-out period of 4-7 days on placebo with lorazepam and/or nitrazepam if necessary, patients were randomly assigned to a daily dose of milnacipran 50 mg, milnacipran 100 mg or amitriptyline 150 mg reached on the 5th day and then stable over a 4-week period, with weekly assessments by means of the Montgomery and Asberg depression scale, the Hamilton depression scale, the Clinical Global Impressions (CGI) and the Target Emergent Signs and Symptoms. Results showed significant superiority of both milnacipran 100 mg/day and amitriptyline over milnacipran 50 mg/day at the end of the treatment period. However, amitriptyline induced a nonsignificant trend toward more rapid improvement after 2 weeks of treatment, mainly based on items related to insomnia, supporting more sedative properties of amitriptyline as compared to milnacipran. Anticholinergic side-effects were significantly lower with milnacipran than with amitriptyline, explaining why milnacipran 100 mg exhibited at the end of the treatment period, a nonsignificantly better efficacy index on the CGI. Moreover, in contrast to milnacipran, amitriptyline was responsible for a significant decrease in blood pressure and a significant weight gain.

Adult↗
PubMed1983

Amitriptyline and ethanol: pharmacokinetic and pharmacodynamic interaction.

Amitriptyline has clinically important interactions with ethanol. Five healthy volunteers received 25 mg of amitriptyline orally, preceded by one hour and followed for eight hours by oral ethanol (or juice), dosed to achieve and maintain blood ethanol concentrations of 800 mg/l. In the presence of ethanol, amitriptyline free plasma concentrations were increased by a logarithmic mean of 204%, 186% and 127% at 1.5, 2, and 2.5 h, respectively, and amitriptyline free AUC0-8h was increased by 48% +/- 13% (means +/- SEM) (t = 5.21, p less than 0.01). Nortriptyline total AUC0-8h was increased by 26.6% +/- 12% (means +/- SEM) (t = 2.21, p less than 0.09). At the time of peak amitriptyline plasma concentrations, mean postural sway was increased over baseline by 92% with, and 2% without ethanol; likewise, mean short term memory (word recall) was decreased over baseline by 71% with, and 37% without ethanol. Ethanol increases free amitriptyline plasma concentrations most dramatically during the period of drug absorption; this is due to a decrease in amitriptyline hepatic clearance, resulting in decreased first-pass extraction. Together with the pharmacodynamic interaction, the kinetic changes provide a rationale for the toxicity of this combination and its deleterious effects on psychomotor skills.

Adult↗
PubMed1983

Analgesic properties of meperidine, amitriptyline and phenelzine in mice.

Sixty-three white Swiss Webster mice were divided into seven equal groups. Their tolerance to pain (heat applied to the tail by a test tube containing hot water at a temperature measured by telethermometry) was assessed before and after intraperitoneal injection of (1) physiologic saline; (2) meperidine 14 micrograms X g-1; (3) amitriptyline 6 micrograms X g-1 (4) amitriptyline 12 micrograms X g-1; (5) phenelzine 1.5 micrograms X g-1; (6) phenelzine 3 micrograms X g-1; and (7) amitriptyline 6 micrograms X g-1 plus phenelzine 1.5 micrograms X g-1. All post-injection tests were conducted 45 and 90 minutes after administration, and repeated 24 hours later. No significant difference in pain threshold was noted in any pre-injection test or in any test conducted with physiologic saline. By 90 minutes post-injection, all groups receiving drugs developed increased tolerance to pain. Mice which had received phenelzine plus amitriptyline, or either dose of phenelzine were more tolerant to pain for up to 24 hours than mice which had received physiologic saline. The most marked increases in tolerance to pain were seen with 1.5 micrograms X g-1 and 3 micrograms X g-1 of phenelzine and phenelzine plus amitriptyline. However, phenelzine was more effective and had a longer-lasting effect than either dose of amitriptyline, or meperidine. The combination of phenelzine plus amitriptyline was no more effective than phenelzine alone.

Amitriptyline↗
PubMedDate not supplied

Comparison of two approaches to amitriptyline dose individualisation.

Individualisation of an amitriptyline dose regimen offers substantial advantages over non-individualised treatment. In our study, we have compared both clinical effects, adverse effects and plasma steady-state concentrations of amitriptyline in 15 patients with major depressive disorder divided in three groups; (i) patients in group A were taking non-individualised doses of amitriptyline; (ii) patients in group B were taking doses of amitriptyline individualised by modified Bayesian method; and (3) patients in group C were taking doses of amitriptyline individualised by the multiple point method. The treatment course was 8 weeks long, in the setting of a psychiatric clinic. The patients in group A were taking significantly higher doses throughout the treatment course; the initial doses for the patients in group B were higher than doses for the patients in group C, but after corrections based on measured steady-state plasma concentrations they became similar. While Hamilton score descended uniformly in all three groups, both adverse effects and steady-state plasma concentrations of amitriptyline were higher in non-individualised group during the whole treatment course. The results of our study suggest that the multiple points method is the most precise, but tedious and not practical. The modified Bayesian method with correction based on first measured plasma steady-state concentration of amitriptyline offers similar therapeutic outcome and adverse effects score combined with low cost and being easy-to-use.

Adult↗
PubMed2002

Effects of low power laser and low dose amitriptyline therapy on clinical symptoms and quality of life in fibromyalgia: a single-blind, placebo-controlled trial.

The purpose of this study was to examine the effectiveness of low power laser (LPL) and low-dose amitriptyline therapy and to investigate effects of these therapy modalities on clinical symptoms and quality of life (QOL) in patients with fibromyalgia (FM). Seventy-five patients with FM were randomly allocated to active gallium-arsenide (Ga-As) laser (25 patients), placebo laser (25 patients), and amitriptyline therapy (25 patients). All groups were evaluated for the improvement in pain, number of tender points, skin fold tenderness, morning stiffness, sleep disturbance, muscular spasm, and fatigue. Depression was evaluated by a psychiatrist according to the Hamilton Depression Rate Scale and DSM IV criteria. Quality of life of the FM patients was assessed according to the Fibromyalgia Impact Questionnaire (FIQ). In the laser group, patients were treated for 3 min at each tender point daily for 2 weeks, except weekends, at each point with approximately 2 J/cm(2) using a Ga-As laser. The same unit was used for the placebo treatment, for which no laser beam was emitted. Patients in the amitriptyline group took 10 mg daily at bedtime throughout the 8 weeks. Significant improvements were indicated in all clinical parameters in the laser group (P = 0.001) and significant improvements were indicated in all clinical parameters except fatigue in the amitriptyline group (P = 0.000), whereas significant improvements were indicated in pain (P = 0.000), tender point number (P = 0.001), muscle spasm (P = 0.000), morning stiffness (P = 0.002), and FIQ score (P = 0.042) in the placebo group. A significant difference was observed in clinical parameters such as pain intensity (P = 0.000) and fatigue (P = 0.000) in favor of the laser group over the other groups, and a significant difference was observed in morning stiffness (P = 0.001), FIQ (P = 0.003), and depression score (P = 0.000) after therapy. A significant difference was observed in morning stiffness (P = 0.001), FIQ (P = 0.003), and depression (P = 0.000) in the amitriptyline group compared to the placebo group after therapy. Additionally, a significant difference was observed in depression score (P = 0.000) in the amitriptyline group in comparison to the laser group after therapy. Our study suggests that both amitriptyline and laser therapies are effective on clinical symptoms and QOL in fibromyalgia and that Ga-As laser therapy is a safe and effective treatment in cases with FM. Additionally, the present study suggests that the Ga-As laser therapy can be used as a monotherapy or as a supplementary treatment to other therapeutic procedures in FM.

Adult↗
PubMed1996

Amitriptyline inhibits the G protein and K+ channel in the cloned thyroid cell line.

We have reported that thyroid K+ channel is activated by extracellular application of the thyroid-stimulating hormone (TSH) using single channel recording method performed on cloned normal rat thyroid cell (FRTL-5) membrane. Treatment of dibutyryladenosine cyclic monophosphate (Bt2 cAMP) also activated the TSH-dependent K+ channel. These findings indicate that the thyroid K+ channel is activated through the TSH-adenosine cyclic monophosphate (cAMP)-protein kinase A system. We examined the effects of amitriptyline on TSH-guanosine triphosphate binding protein (G protein)-adenylate cyclase-cAMP-K+ channel system in the cloned normal rat thyroid cell line FRTL-5. Amitriptyline inhibited the cAMP production induced by TSH. Amitriptyline also inhibited the cAMP production induced by cholera toxin, indicating that amitriptyline inhibited the thyroid G protein. Amitriptyline had no effect on TSH-receptor binding and cAMP production by forskolin (adenylate cyclase stimulator). Amitriptyline inhibited the K+ channel activation by cAMP, indicating that the suppressing mechanism is not the inhibition of TSH receptor or G protein but the direct suppression of K+ channel. It was concluded that amitriptyline inhibited the thyroid G protein and K+ channel.

Amitriptyline↗
PubMed1996

Amitriptyline effectively relieves neuropathic pain following treatment of breast cancer.

The effectiveness of amitriptyline in relieving neuropathic pain following treatment of breast cancer was studied in 15 patients in a randomised, double-blind placebo-controlled crossover study. The dose was escalated from 25 mg to 100 mg per day in 4 weeks. The placebo and amitriptyline phases were separated by a 2-week wash-out period. Visual analogue and verbal rating scales were used for the assessment of pain intensity and pain relief. Other measures included the number of daily activities disturbed by the pain, the Finnish McGill Pain Questionnaire, adverse effects, anxiety, depression, pressure threshold and grip strength. Amitriptyline significantly relieved neuropathic pain both in the arm and around the breast scar. Eight out of 15 patients had a more than 50% decrease in the pain intensity ('good responders') with a median dose of 50 mg of amitriptyline. The 7 patients who had a less than 50% effect had drug concentrations equaling those of the good responders. The 'poor responders' reported significantly more adverse effects with amitriptyline and placebo than the good responders. It is concluded that amitriptyline effectively reduced neuropathic pain following treatment of breast cancer. However, the adverse effects of amitriptyline put most of the patients off from using the drug regularly.

Adult↗
PubMed2006

Amitriptyline suppresses neuroinflammation and up-regulates glutamate transporters in morphine-tolerant rats.

The present study was performed to evaluate the effects of the tricyclic antidepressant amitriptyline on morphine tolerance in rats. Male Wistar rats were implanted with two intrathecal (i.t.) catheters with or without a microdialysis probe, then received a continuous i.t. infusion of saline (control) or morphine (15 microg/h) and/or amitriptyline (15 microg/h) for 5 days. The results showed that amitriptyline alone did not produce an antinociceptive effect, while morphine alone induced antinociceptive tolerance and down-regulation of spinal glutamate transporters (GLAST, GLT-1, and EAAC1) in the rat spinal cord dorsal horn. Co-administration of amitriptyline with morphine attenuated morphine tolerance and up-regulated GLAST and GLT-1 expression. On day 5, morphine challenge (10 microg/10 microl) resulted in a significant increase in levels of the excitatory amino acids (EAAs), aspartate and glutamate, in CSF dialysates in morphine-tolerant rats. Amitriptyline co-infusion not only markedly suppressed this morphine-evoked EAA release, but also preserved the antinociceptive effect of acute morphine challenge at the end of infusion. Glial cells activation and increased cytokine expression (TNFalpha, IL-1beta, and IL-6) in the rat spinal cord were induced by the 5-day morphine infusion and these neuroimmune responses were also prevented by amitriptyline co-infusion. These results show that amitriptyline not only attenuates morphine tolerance, but also preserves its antinociceptive effect. The mechanisms involved may include: (a) inhibition of pro-inflammatory cytokine expression, (b) prevention of glutamate transporter down-regulation, and even up-regulation of glial GTs GLAST and GLT-1 expression, with (c) attenuation of morphine-evoked EAA release following continuous long-term morphine infusion.

Amino Acid Transport System X-AG↗
PubMed2002

Involvement of adenosine in the anti-allodynic effect of amitriptyline in streptozotocin-induced diabetic rats.

Recent observations suggest the involvement of adenosine in the peripheral antinociceptive effect of amitriptyline in nerve-injury-induced neuropathic pain. The aim of the present investigation was to evaluate, firstly, the peripheral and systemic effects of amitriptyline on tactile allodynia in the streptozotocin (STZ)-induced diabetic rat model of neuropathic pain and, secondly, whether caffeine coadministration affects the actions of amitriptyline. Diabetes was induced by a single intraperitoneal (i.p.) injection of STZ (50 mg/kg), and tactile allodynia was detected by application of von Frey filaments to the ventral surface of the hindpaw. Both systemic (0.5-2.0 mg/kg, i.p.) and peripheral (10-100 nmol, subcutaneously (s.c.)) administration of amitriptyline were found to produce increases in paw withdrawal thresholds, at higher doses. Coadministration of caffeine (5 mg/kg, i.p.; 1500 nmol, s.c.), at doses which produced no effect on its own, partially reversed systemic and local anti-allodynic effects of amitriptyline. These results indicate an anti-allodynic effect of both peripheral and systemic amitriptyline, and suggest the involvement of endogenous adenosine in the action of amitriptyline in this rat model of painful diabetic neuropathy. These data also suggest that topical application of tricyclic antidepressants may be useful in treating neuropathic pain in diabetics.

Adenosine↗
PubMed2000

Gabapentin vs. amitriptyline in painful diabetic neuropathy: an open-label pilot study.

The objective of this study was to compare the efficacy and tolerability of gabapentin and amitriptyline monotherapy in painful diabetic neuropathy. This was a 12-week, open-label, prospective, randomized trial. Twenty-five type-II diabetic patients with pain attributed to diabetic neuropathy and a minimum score of 2 on a pain intensity scale ranging from 0 (no pain) to 4 (excruciating pain) were randomized to receive either gabapentin, titrated from 1,200 mg/day to a maximum of 2,400 mg/day, or amitriptyline, titrated from 30 mg/day to a maximum of 90 mg/day. Both drugs were titrated over a 4-week period and maintained at the maximum tolerated dose for 8 weeks. The main outcome measures were weekly pain intensity and paresthesia intensity, measured on two categorical scales. Thirteen patients received gabapentin and 12 received amitriptyline. All 25 patients completed the trial. Gabapentin produced greater pain reductions than amitriptyline (mean final scores were 1.9 vs. 1.3 points below baseline scores; P = 0.026). Decreases in paresthesia scores also were in favor of gabapentin (1.8 vs. 0.9 points; P = 0. 004). Adverse events were more frequent in the amitriptyline group than in the gabapentin group: they were reported by 11/12 (92%) and 4/13 (31%) of patients, respectively (P = 0.003). Side effects were the main limiting factor preventing dose escalation. Gabapentin produced greater improvements than amitriptyline in pain and paresthesia associated with diabetic neuropathy. Additionally, gabapentin was better tolerated than amitriptyline. Further controlled trials are needed to confirm these preliminary results.

Acetates↗
PubMed2003

Selective decrease in serotonin synthesis rate in rat brainstem raphe nuclei following chronic administration of low doses of amitriptyline: an effect compatible with an anti-migraine effect.

The effects of chronic, low-dose amitriptyline on serotonin (5-HT) synthesis rate were measured in rat brain using autoradiography and the trapping of alpha-[14C]-methyl-L-tryptophan (alpha-[14C]-MTrp). Rats received amitriptyline (2 mg/kg per day) or saline via intraperitoneal osmotic minipumps for 21 days. Amitriptyline had no effect on any physiological parameters measured, or on free or total plasma tryptophan levels. However, amitriptyline exerted selective decreases of 15% and 17% (P < 0.001) in serotonin synthesis rates in the dorsal and median raphe nuclei, respectively. There was no reduction in any of the projection areas studied, including the cerebral cortex, hippocampus, thalamus, hypothalamus or striatum. The data suggest that chronic low doses of amitriptyline can lead to sustained 5-HT re-uptake inhibition selectively in the raphe nuclei, an effect compatible with tonic activation of 5-HT(1A) autoreceptors and inhibition of 5-HT synthesis. The failure of chronic amitriptyline treatment to affect 5-HT synthesis rate in the projection areas may ensure an adequate regulation of pain pathways implicated in migraine headache, an effect possibly related to amitriptyline anti-migraine efficacy.

Amitriptyline↗
PubMed1975

Noxiptilin (Agedal)--a new tricyclic antidepressant with a faster onset of action? A double-blind, multicentre comparison with amitriptyline.

Five psychiatric hospitals in Norway took part in this double blind clinical trial, in which noxiptilin (Agedal) was compared with amitriptyline in hospitalized patients with primary depressive illness. According to total randomization, each patient received either noxiptilin or amitriptyline in semiflexible dosage, usually to a maximum dialy dose of 200-250 mg, for at least three, and possibly six weeks. Thirty patients received noxiptilin and 32 received amitriptyline for at least three weeks. The "total" improvement was assessed in two different ways: 1) By direct global assessment; according to this method, there was a non-significant tendency towards greater improvement on amitriptyline after three and sex weeks, in female and male patients alike. 2) By percentage reduction in total score on Hamilton's rating scale for depression; according to this method, there was a significantly greater improvement on noxiptilin after one week in female but not in male patients. After 2, 3 and 6 weeks there were no significant differences. Thus, this trial seems to support earlier claims that noxiptilin has a faster onset of action than amitriptyline. The two drugs did not differ significantly in their effect on any single symptom, nor in their effect on different types of depression. Both drugs had a better effect in patients with duration of present illness less than three months, than in patients with a duration longer than three months. Noxiptilin had a significantly better effect than amitriptyline in patients with insidious onset of present illness, whereas there was a strong (but non-significant) tendency for a better effect of amitriptyline in patients with a more acute onset of illness. No satisfactory explanation can be offered for this unexpected finding.

Adult↗
PubMed1979

Clinical profile and serum concentration of viloxazine as compared to amitriptyline.

The antidepressive effect of viloxazine (300 mg/d) was investigated during three weeks in 41 patients with depressive syndromes requiring drug-treatment against amitriptyline (150 mg/d), using a controlled double-blind design. Viloxazine differs from amitriptyline by selective inhibition of norepinephrine re-uptake, whereas amitriptyline acts also on serotonin re-uptake. Psychopathological changes were documented by means of the Hamilton Depression Rating Scale, the Bf-S (v. Zerssen), the AMDP-System, and videotaped recordings. Besides routine clinical-chemical tests, the serum concentrations of viloxazine and partly of amitriptyline were determined. Repeated EEG-recordings were evaluated by spectral analysis. The number of global responders and non-responders -- defined according to the final HDRS-scores -- was equally distributed between the two drug-groups. The AMDP-evaluation suggests that viloxazin has a somewhat more marked and more rapid effect on symptoms of retardation, whereas amitriptyline acts predominantly on depressive mood, disturbances of sleep and vital feelings. The EEG-profile of both drugs was similar to the spectral changes seen under tricyclic antidepressants, through only the viloxazine-induced changes reached statistical significance on the 10th and 20th day, the variability of the EEG-recordings being greater in the amitriptyline group. The viloxazine blood levels showed a remarkably low inter- and intraindividual variance. Steady state was reached at day 5 at the latest. Amitriptyline serum concentrations still increased between the 10th and the 21st day. The average blood concentration of viloxazine was higher in the responder- than in the non-responder-group.

Adult↗
PubMed2000

Double-blind, multicenter comparative study of sertraline versus amitriptyline in outpatients with major depression.

OBJECTIVE: To compare the efficacy and safety of sertraline and amitriptyline in a German outpatient population. METHODS: Patients with Major Depression (DSM-III-R) and HAM-D (21 items) > or = 21 in 19 German centers received double-blind treatment with sertraline (initial dose 50 mg, titration up to 100 mg) or amitriptyline (75 mg, up to 150 mg) over 6 weeks. HAM-D (21 items), HAM-D Bech, CGI, DSI and SDS were evaluated for the efficacy analysis. FSUCL (Fischer Somatic and Undesired Effects Check List) and spontaneously reported adverse events were used for safety analysis. RESULTS: Of the 240 patients enrolled in the study, 205 (100 sertraline; 105 amitriptyline) were evaluable for efficacy. No statistically significant differences were detected between the two groups in the ITT and ATP efficacy analyses. Response, defined as score 1 (very much improved) or 2 (much improved) of the CGI improvement score, was 76% in the sertraline and 81% in the amitriptyline group (efficacy evaluable patients = ATP population). In the structured FSUCL, the side-effect burden (FSUCL score >2 for drug related symptoms) was significantly higher in the amitriptyline group at all follow up visits (p<0.05). CONCLUSION: Both sertraline and amitriptyline are suitable for the treatment of Major Depression; sertraline is comparable to amitriptyline with regard to efficacy, and offers the additional benefit of a more favorable safety profile.

Adult↗
PubMed2004

Amitriptyline for inpatients and SSRIs for outpatients with depression? Systematic review and meta-regression analysis.

BACKGROUND: Although the selective serotonin reuptake inhibitors (SSRIs) are widely used as first-line agents in depression, amitriptyline, a reference tricyclic (TCA) agent, has the edge in terms of efficacy over control antidepressants (ADs), but it is not clear whether this advantage can be attributed to a more favourable profile in inpatients, but not in outpatients, with depression. The aim of this study was to investigate the contribution of study setting on outcome in clinical trials comparing amitriptyline with any other AD. METHODS: A systematic review and meta-regression analysis of amitryptiline randomised clinical trials was carried out. The electronic search yielded 181 randomised clinical trials, 47% enrolling inpatients and 53% outpatients with depression. RESULTS: Both on a dichotomous and continuous out-come, amitriptyline was more effective than control agents in in-patients [Peto odds ratio (OR): 1.22, 95%, Confidence Interval (CI): 1.04, 1.42; Standardised Mean Difference (SMD): 0.28, 95 %,Cl: 0.08, 0.46], but not in outpatients (Peto OR: 1.01, 95%, CI: 0.88,1.17; SMD: 0.10,95% CI: -0.02,0.23). Among inpatients amitriptyline was significantly more effective than TCA and nonsignificantly more effective than the SSRIs. Among outpatients no statistically significant differences emerged between amitriptyline and TCA and between amitriptyline and the SSRIs. Amitriptylinewas less well tolerated than control agents in outpatients (Peto OR: 0.90, 95%, CI: 0.81, 0.99), but not in inpatients (Peto OR:1.09, 95% CI: 0.95, 1.25). CONCLUSIONS: These data suggest that a reasonable approach could be the first-line prescription of newer agents in the routine outpatient care of depressive subjects, and the use of amitriptyline in inpatients with severe depression.

Adrenergic Uptake Inhibitors↗
PubMed1986

Femoxetine and amitriptyline in general practice: a randomized double-blind group comparison.

Patients with a depressive illness with 4 major symptoms of depression and a score of at least 17 on the Hamilton Depression Scale (1-17) (HDS) were allocated to a randomized double-blind group comparative study in general practice. After retrospective analysis, all 81 patients except one were characterized as suffering from a 'Definite Major Depressive Disorder', as defined by Spitzer et al. (1978). After 6 weeks of treatment with a daily dosage of 600 mg femoxetine or 150 mg amitriptyline, no statistically significant differences between the 2 treatment groups were observed, either when using the HDS or the clinical global assessment scale. Confidence limits of 95% for differences between therapeutic effect showed a non-significant tendency in favour of amitriptyline. During treatment, there were statistically significant differences in the reduction of HDS score between the 2 treatments in week 2. These differences were the result of amitriptyline's significantly greater effect on the 3 sleep items at week 2, as indicated by the results of single item analysis. Drop out rates due to side effects were between 14-15% in both treatment groups. Of the patients treated with femoxetine, 38% experienced no side effects, compared to 14% of patients treated with amitriptyline. Nausea was the side effect most commonly reported by patients treated with femoxetine, whereas a significantly greater frequency of anticholinergic side effects was recorded during treatment with amitriptyline (P less than 0.05). Unlike amitriptyline, femoxetine did not increase body weight. Treatment with the active drug was continued after the trial period in 14 and 18 patients in the femoxetine and amitriptyline groups respectively.

Adolescent↗
PubMed1985

Single oral dose pharmacokinetics of amitriptylinoxide and amitriptyline in humans.

Eleven healthy volunteers were examined in a pharmacokinetic study. After oral administration of 50 mg amitriptylinoxide or 50 mg amitriptyline the plasma levels of amitriptylinoxide and its main metabolites amitriptyline and nortriptyline were investigated over 24 hours. The results indicate that amitriptylinoxide is more rapidly absorbed than amitriptyline and eliminated with a mean half-life of 1.5 hours. The change with time in the levels of amitriptyline formed from the oxide is similar to that of amitriptyline after ingestion of amitriptyline. However, the plasma concentration of amitriptylinoxide, reflected by the area under the time curve (AUC), exceeds that of its metabolite amitriptyline twelvefold.

Administration, Oral↗