Reboxetine is an anti-depressant with a unique group of actions that tackle anxiety and stimulate the mind
Reboxetine is an anti-depressant known as a selective noradrenaline re-uptake inhibitor (SNRI). When depression occurs there may be a decreased amount of a chemical called noradrenaline released from nerve cells in the brain. A release of noradrenaline acts to lighten mood. So when noradrenaline is reabsorbed into the nerve cells, it no longer can affect mood.
Reboxetine works by preventing this re-absorption of noradrenaline back into the nerve cells. Therefore, it helps prolong the mood-lightening effect of any released noradrenaline, which helps relieve depression.
Elderly people suffering from low mood, sleep disturbances, low energy levels and poor concentration could benefit from Reboxetine. As the elderly are particularly susceptible to the potential side effects of current antidepressants (due to age-related physiologic changes) Reboxetine may suit them better.
Studies found that patients felt "much" to "very much" improved by Reboxetine. It was well tolerated by the majority of patients and efficacy outweighed side effects in 75% of patients.
As a selective noradrenaline reuptake inhibitor, Reboxetine has been found to be an effective and safe anti-depressant. Furthermore, Reboxetine restores a patients' social functioning, producing a better quality of remission than fluoxetine.
Reboxetine can also be used as a stimulant. In studies with narcolepsy (uncontrolled daytime sleeping) Reboxetine was noted to exert stimulant and anticataplectic effects.
Dosage:
Initial dose is 4mg once or twice a day.
Side effects:
Headache, dry mouth, urinary hesitance, constipation, early awakening.
Caution:
Like most anti-depressants, this drug could interfere with other anti-depressants, particularly MAO inhibitors (including Gerovital-H3) and also with noradrenaline enhancers, such as Adrafinil and Modafinil, and therefore any combined use must only take place under the guidance of a physician. Reboxetine reduce your ability to drive or operate machinery safely. Do not drive or operate machinery until you know how this medicine affects you and you are sure it won't affect your performance.
The Noradrenaline Factor
Whilst serotonin plays a vital role in mood, noradrenaline is essential to drive and motivation. Chronically depressed individuals typically have dysfunctional and atypical noradrenergic systems, particularly with regard to alpha-2 and beta-adrenoceptors. Reboxetine (trade name Edronax ®), is a recent anti-depressant development from the pharmaceutical company Pharmacia & UpJohn. It is a selective noradrenaline reuptake inhibitor (NARI) and it has shown itself to be effective in both the short term (4-8 weeks) and long-term (up to 12-months) for the treatment of depression. Apart from regulating energy, drive and motivation, the noradrenaline neurotransmitter is also involved in regulating the sleep-wake cycle, food intake, endocrine function and peripheral sympathetic function. Dr. Borson from Pharmacia & UpJohn stated 'it is possible that movement, initiation speed and the stamina of individuals is conditioned in part by noradrenergic mechanisms.'
Reboxetine- Clinical Trials
A long-term open label study was conducted with 139 people whose mean age was 74, two thirds of the participants were women. It was discovered that those patients who improved within a 6-week period maintained their gains over the year. Nearly 88% of the patients improved their depression and reboxetine was well tolerated. In fact improvements were noted to be better in severe depressive cases than those that could normally be achieved with SSRI's.
A further extensive study by Pharmacia & UpJohn with 549 patients showed that reboxetine was as effective as Prozac ® within an 8-week period. Patients in the double-blind placebo controlled study taking reboxetine had a 19-point drop in depression scores compared to a 17-point drop for Prozac ®. Side effects with reboxetine were noted as dry-mouth, insomnia and constipation. The study was conducted at the Hospital Clinic in Barcelona, Spain by Dr. Juan Massana who stated; 'these studies provide important information on the role that [noradrenaline] plays in depression and a possible treatment option for the many patients around the world who suffer from depression.'
There have been numerous other studies with up to 2000 patients taking part in double-blind placebo-controlled conditions. They all indicate that reboxetine is an effective anti-depressant with few and usually minor side effects. Reboxetine has proven to be effective in short term use and equivalent if not better than the 'standard' SSRI drug interventions.
Reboxetine- Dosages, Contraindications and Side Effects
The most noted side effects of reboxetine use have been dry mouth, insomnia, constipation, increased sweating, tachycardia and vertigo. Although it has proven to be safer than the SSRI's, its use in patients with severe heart conditions is not advised. Furthermore, reboxetine should only be given under close supervision to subjects with a history of seizure disorders. As with nearly all anti-depressants switches from mania to hypomania have occurred, thus patients who suffer with chronic depression and suicidal tendencies require close supervision. At high dosages urinary difficulties in passing water have also been noted in a few rare cases, as such the maker recommends that persons with an enlarged prostate and glaucoma (increased pressure in the eyes) avoid use.
Ketoconazole has been shown to increase the concentration of reboxetine, therefore care may be advised if ingesting these two substances. MAO inhibitors are also not advised to be taken with reboxetine, as well as concomitant use of tricyclic, SSRI drugs and lithium; this is because potential reactions have not yet been studied in clinical trials. No tests have been conducted in pregnancy and therefore pregnant and lactating women must avoid use and as is normal with nearly all drugs, persons suffering from severe liver or kidney disorders should also avoid use, (to save repetition please apply these statements to all the drugs mentioned in this article). The maker also suggests the avoidance of certain types of anti-biotics including erythromycin, fluvoxamine and anti-fungals such as fluconazole, flecainide and cyclosporin. Interestingly in the makers drug-insert it also suggests avoidance of ergot derivative drugs (such as hydergine ®, bromocriptine or nicergoline), but within the time constraints for this article we couldn't find the reason why.
Standard dosages have been 4mg to 8mg per day, up to 12mg (20mg per day were used for a few weeks in some trials), however as most side effects begin to appear at dosages in excess of 8mg per day there is probably little need to exceed 8mg per day.
"....Reboxetine (Edronax) is a relatively well-tolerated, relatively selective "noradrenergic" agent. Crudely, whereas serotonin plays a vital role in anxiety and mood, noradrenaline is essential to maintaining drive, self-assertiveness and the capacity for reward. There's a fair bit of evidence that chronically depressive people have dysfunctional and atypical noradrenergic systems - particularly their alpha 2- and beta-adrenoceptors. Reboxetine itself typically doesn't have the disruptive effects on cognitive function or psychomotor performance common to older, tricyclic clinical mood-brighteners - though alas antimuscarinic effects are still not completely absent. Indeed for one sub-population of depressives, the new NorAdrenaline Reuptake Inhibitors (NARIs) are possibly under-used. Unfortunately, catecholaminergic strategies to combat depression were eclipsed in the late 1980s and 1990s by the marketing hype surrounding selective serotonin reuptake inhibitors (SSRIs).
Reciprocal interactions between the different monoamine systems make it hard to target one neurotransmitter system without triggering a cascade of effects on the others. But NARIs - and "dopaminergics" like amineptine (Survector) - may be especially useful in drive-deficient "anergic" states where the capacity for sustained motivation is lacking; in the treatment of "retarded" depression; and for melancholic depressives with a poor ability to cope with stress. Anxious depressives, on the other hand, may do better on Servier's neuroprotective and anxiolytic antidepressant tianeptine (Stablon), though comparative clinical trials are lacking.
Reboxetine may be safely combined with an SSRI, though there is evidence that NARIs themselves indirectly enhance central serotonin function by a mechanism that doesn't depend on reuptake inhibition. More surprisingly perhaps, preliminary studies suggest reboxetine can actually reverse tranylcypromine-induced hypertensive crises. The "cheese effect" is usually triggered by ingesting tyramine-rich foods. Thus NARIs plus MAOIs may prove a potent form of combination-therapy if other options fail. Newly-licensed (2006) EMSAM, the transdermal selegiline patch, is probably the safest choice of MAOI.
Reboxetine may also be used off-label to treat low back pain and fibromyalgia.
By early 2007, reboxetine was licensed worldwide in over 60 countries. In May 2001, however, the FDA declined Pharmacia's license application for the North American market. The grounds for the decision have not been officially disclosed... "
Reboxetine is an antidepressant drug used in the treatment of clinical depression, panic disorder and ADD/ADHD. Its mesylate (i.e. methanesulfonate) salt is sold under tradenames including Edronax, Norebox, Prolift, Solvex or Vestra. Reboxetine has two chiral centers, but it only exists as two enantiomers, (R,R)-(-)- and (S,S)-(+)-reboxetine.[3]//
Mode of action
Unlike most antidepressants on the market, reboxetine is a norepinephrine reuptake inhibitor (NRI); it does not inhibit the reuptake of serotonin, therefore it can be safely combined with an SSRI.
Side effects
Common side effects of reboxetine include: dry mouth, constipation, headache, drowsiness, dizziness, excessive sweating and insomnia. Hypertension has been infrequently seen.
In 4 to 8% of all patients treated the medication has to be discontinued due to following reasons (percentages represent mean values):
insomnia 1.3%
excessive sweating 1.1%
vertigo/hypotension and paraesthesia 0.8%
dizziness, impotence, and other urological problems 0.5% each
Some other rare side effects include anxiety, loss of appetite, loss of libido, urinary retention in men, pain on ejaculation, increased orgasm intensity, and premature/quickened ejaculation.
Reboxetine is very well tolerated. So far no attributable fatalities have been noted.
Metabolism
Both the (R,R)-(-) and (S,S)-(+)-enantiomers of reboxetine are predominantly metabolized by the CYP3A4 isoenzyme.[4] The primary metabolite of reboxetine is O-desethylreboxetine, and there are also three minor metabolites—Phenol A, Phenol B, and UK1, Phenol B being the most minor.[4]
Interactions with other medications
Because of its reliance on CYP3A4, reboxetine O-desethylation is markedly inhibited by papaverine and ketoconazole.[4]
According to Weiss et al, reboxetine is an intermediate-level inhibitor of P-glycoprotein, which gives it the potential to interact with ciclosporin, tacrolimus, paroxetine, sertraline, quinidine, fluoxetine, fluvoxamine.[5]
The sedative properties of lorazepam can be increased because reboxetine interferes with its excretion.
History
By mid-2001, reboxetine was licensed worldwide in over 50 countries, including Italy, Germany and the United Kingdom. In May 2001, however, the Food and Drug Administration declined Pharmacia's license application for the American market. As such it is yet to be available in the United States.
Reboxetine is a NorAdrenaline Reuptake Inhibitor (NARI) that is approved in over 50 countries as an antidepressant. In May 2001, the FDA declined the approval of reboxetine for the US.
1. Reboxetine efficacy in major depression [/font]
2. Reboxetine[font="Arial"] effect on social behavior
3. Reboxetine effect on panic disorder
4. Reboxetine does it offer advantages over SSRIs?
5. Reboxetine role in antidepressant therapy
6. Reboxetine efficacy and tolerability
7. Reboxetine clinical pharmacologic profile
8. Reboxetine Inhibiting noradrenaline and serotonin reuptake
9. Reboxetine and depression in the elderly
10. Reboxetine with severe major depressive disorder
11. Reboxetine clinical efficacy in major depression
12. Reboxetine effects on Hamilton Depression Rating Scale
13. Reboxetine comparison with fluoxetine
14. Reboxetine versus fluoxetine, impact on social functioning
15. Reboxetine versus fluoxetine, differential effects
16. Reboxetine prevents relapse in major depression
17. Reboxetine efficacy compared with imipramine
18. Noradrenaline reuptake inhibition
19. Antidepressants noradrenergic versus serotonergic
20. Reboxetine in the treatment of bulimia
21. Reboxetine hemodynamic effects in healthy males
22. Reboxetine effects of antidepressant therapy
23. Reboxetine place in antidepressant therapy
24. Reboxetine stimulant effects in patients with narcolepsy
25. Reboxetine selective noradrenaline reuptake inhibitor (NARI)
Reboxetine in Healthy Adults
Br J Psychiatry. 2007 Jun;190:531-2.
Short-term antidepressant treatment and facial processing. Functional magnetic resonance imaging study.
Norbury R, Mackay CE, Cowen PJ, Goodwin GM, Harmer CJ. University of Oxford Centre for Clinical Magnetic Resonance Research, MRS Unit, John Radcliffe Hospital, Headington, Oxford OX3 9DU, UK. raymond.norbury@psych.oxford.ac.uk
We used functional magnetic resonance imaging to investigate the effects of short-term treatment with reboxetine, a selective noradrenaline reuptake inhibitor, on emotional facial processing in healthy volunteers. Reboxetine was associated with a reduced amygdala response to fearful faces and increased activation to happy v. neutral facial expressions in the right fusiform gyrus, relative to placebo treatment and in the absence of changes in mood. Our results show that reboxetine modulates the neural substrates of emotional processing, highlighting a mechanism by which drug treatment could normalise negative bias in depression and anxiety.
J Neural Transm. 2007 Aug;114(8):1085-9. Epub 2007 Mar 31.
Chronic dose effects of reboxetine on motor skill acquisition and cortical excitability.
Lange R, Weiller C, Liepert J. Department of Neurology, University Freiburg, Freiburg, Germany.
Background. Enhancement of cortical excitability is thought to be beneficial for synaptic plasticity associated with motor skill acquisition. Single dose application of the selective norepinephrine reuptake inhibitor reboxetine (RBX) increases motor cortex excitability. In this study, we tested if a chronic dose application of RBX improved motor skill acquisition and modulated cortical excitability. Methods. The study was randomised, double blind and placebo-controlled. Twelve healthy subjects received four milligram RBX twice a day for four days preceded by two milligram RBX twice a day for two days. Each subject served as his own control. The time interval between the verum and the placebo session was 16 days or more. Measurement of cortical excitability by means of paired pulse transcranial magnetic stimulation (ppTMS) was conducted before and after the motor skill acquisition task in each session. The task was to lift two fingers of the right hand at once while the hand was positioned sprawled out on the table. The movements were self-paced and subjects had to perform as many moves as possible in 60 sec. Between seven blocks of self-paced movements six blocks with 60 single trials at a fixed interstimulus intervall were presented. Two equally difficult versions of the task using different finger combinations were established in order to avoid carry over effects in performance. The finger movements were recorded with a three-dimensional ultrasound movement analysis system (Zebris). Results. All subjects had substantial gain in performance across the selfpaced blocks. Average increase in number of correct moves was 87% (from 27.8 to 51.9). There was no significant difference neither between the versions of the task nor between placebo vs. verum. Also, there was no significant difference between first and second session, indicating that there was no carry over effect in performance. ppTMS revealed no significant differences in cortical excitability between groups. Conclusion. The newly developed skill acquisition task yields robust single subject gain of performance. As the two versions of the task do not interact, it is suitable to be used in cross-over designs. In contrast to studies using single doses of RBX, motor cortex excitability seems to be unaffected in a steady-state induced by repeated drug applications. This could explain why RBX did not modulate motor behavior.
Pharmacopsychiatry. 2006 Sep;39(5):175-9.
Noradrenaline might enhance assertive human social behaviours: an investigation in a flatmate relationship.
Tse WS, Bond AJ. Department of Applied Social Studies, City University of Hong Kong, Tat Chee Ave., Hong Kong. tse.vincent@cityu.edu.hk
OBJECTIVE: The aim of the present study was to explore the role of noradrenaline on the social behaviour of healthy volunteers when they were interacting with a familiar person, their flatmate. Interaction with the flatmate was explored in a cooperative game situation. METHODS: Ten pairs of same-sex healthy volunteer flatmates aged 18-25 years were recruited for the experiment. All volunteers gave written informed consent and the study was approved by the institutional ethical committee. A randomised, double blind, placebo-controlled crossover trial of reboxetine versus placebo was conducted. In each of the 10 pairs of volunteers, one (subject) volunteered to take the tablets and the other (flatmate) received no treatment. Reboxetine (4 mg/bd) and placebo were administered orally as identical capsules for 2 weeks. The subjects were randomly assigned to receive either reboxetine or placebo first and there was a two-week washout period following the first treatment. At baseline and the end of each treatment, they filled in the Beck Depression Inventory (BDI), Social Adapation Self-Evaluation Scale (SASS), and Aggression Questionnaire (AQ). Then, they were instructed to play the Tangrams game. This task elicits face-valid social behaviours such as cooperation, giving commands and unilateral grasps. RESULTS: Analysis of covariance showed that there was a statistical trend for reboxetine treatment to increase commands (p=0.055). CONCLUSION: This study presents preliminary evidence that two weeks' enhancement of noradrenaline transmission induced by reboxetine makes healthy volunteers more self-confident and assertive.
J Psychopharmacol. 2003 Jun;17(2):189-95.
Reboxetine promotes social bonding in healthy volunteers.Tse WS, Bond AJ.
Division of Psychological Medicine, Institute of Psychiatry, King's College London, UK.
Reboxetine is a novel antidepressant with a selective action on noradrenaline. In addition to its efficacy in depression, it has been found to improve social adaptation. The objective of this study was to assess the specific social behavioural effects of reboxetine which might be associated with social adaptation. Ten pairs of healthy volunteers took part in a randomized double-blind, crossover study of 2 weeks treatment with reboxetine (4 mg b.d.) and placebo with a 2-week washout period. In each pair, one person (subject) took the tablets and the other (flatmate) received no treatment. On the last day of each treatment period, the subjects socially interacted with a stranger (a confederate behaving as a responsive person) in a stranger-dyadic social interaction paradigm. After the interaction, subjects played the Mixed-Motive game, which measures cooperative behaviour and communication, with the confederate. Subjects read a short story before and after the social interaction. The flatmates evaluated the social behaviour of the subjects before and at the end of the two treatment periods. On reboxetine, the subjects were rated to be significantly more agreeable and cooperative (passive participant) and less submissive by their flatmates. They showed significantly less eye contact with the confederate in the social interaction paradigm and gave significantly fewer helplessness messages during the game. They spoke faster on the reading task after the social interaction. This study provides evidence that reboxetine increases cooperative social behaviour and increases social drive, which might be important for social adaptation.
Am J Psychiatry. 2004 Jul;161(7):1256-63.
Increased positive versus negative affective perception and memory in healthy volunteers following selective serotonin and norepinephrine reuptake inhibition.
Harmer CJ, Shelley NC, Cowen PJ, Goodwin GM. University Department of Psychiatry, Warneford Hospital, Oxford OX3 7JX, UK.
OBJECTIVE: Antidepressants that inhibit the reuptake of serotonin (SSRIs) or norepinephrine (SNRIs) are effective in the treatment of disorders such as depression and anxiety. Cognitive psychological theories emphasize the importance of correcting negative biases of information processing in the nonpharmacological treatment of these disorders, but it is not known whether antidepressant drugs can directly modulate the neural processing of affective information. The present study therefore assessed the actions of repeated antidepressant administration on perception and memory for positive and negative emotional information in healthy volunteers. METHOD: Forty-two male and female volunteers were randomly assigned to 7 days of double-blind intervention with the SSRI citalopram (20 mg/day), the SNRI reboxetine (8 mg/day), or placebo. On the final day, facial expression recognition, emotion-potentiated startle response, and memory for affect-laden words were assessed. Questionnaires monitoring mood, hostility, and anxiety were given before and after treatment. RESULTS: In the facial expression recognition task, citalopram and reboxetine reduced the identification of the negative facial expressions of anger and fear. Citalopram also abolished the increased startle response found in the context of negative affective images. Both antidepressants increased the relative recall of positive (versus negative) emotional material. These changes in emotional processing occurred in the absence of significant differences in ratings of mood and anxiety. However, reboxetine decreased subjective ratings of hostility and elevated energy. CONCLUSIONS: Short-term administration of two different antidepressant types had similar effects on emotion-related tasks in healthy volunteers, reducing the processing of negative relative to positive emotional material. Such effects of antidepressants may ameliorate the negative biases in information processing that characterize mood and anxiety disorders. They also suggest a mechanism of action potentially compatible with cognitive theories of anxiety and depression.
Reboxetine In Panic Disorder
J Clin Psychiatry. 2002 Jan;63(1):31-7.
Reboxetine, a selective norepinephrine reuptake inhibitor, is an effective and well-tolerated treatment for panic disorder.
Versiani M, Cassano G, Perugi G, Benedetti A, Mastalli L, Nardi A, Savino M. Institute of Psychiatry, Federal University of Rio de Janeiro, Brazil.
BACKGROUND: Tricyclic antidepressants and selective serotonin reuptake inhibitors (SSRIs) as well as benzodiazepines have been shown to be effective for the treatment of panic disorder. The introduction of SSRIs has enabled a greater understanding of the role of serotonin in the etiology of panic disorder; however, the role of norepinephrine has been more challenging to ascertain. The aim of this study was to determine the efficacy and tolerability of reboxetine, a novel selective norepinephrine reuptake inhibitor, in patients with panic disorder with and without agoraphobia. METHOD: Eighty-two patients (aged 18-65 years) with DSM-III-R panic disorder, with or without agoraphobia, were randomly assigned to receive 6 to 8 mg/day of reboxetine (42 patients) or placebo (40 patients) for 8 weeks in this placebo-controlled, parallel-group, double-blind clinical trial. RESULTS: Of the 82 patients enrolled in the trial, 75 were considered in the analysis (37 patients in the reboxetine group and 38 patients in the placebo group). At last assessment, there was a significant reduction in the mean number of panic attacks (range, 9.3-1.2) and phobic symptoms (range, 8.1-3.2) in the reboxetine group compared with the placebo group (ranges, 8.5-5.8 and 7.7-5.2, respectively; p < .05). Improvement in Hamilton Rating Scale for Depression, Hopkins Symptom Checklist-90, and Sheehan Disability Scale scores were also greater in the reboxetine group compared with the placebo group. Adverse events reported more frequently with reboxetine than placebo included dry mouth (36% vs. 16%), constipation (27% vs. 22%), and insomnia (26% vs. 22%). CONCLUSION: Reboxetine was effective and well tolerated in the treatment of panic disorder.
Reboxetine In PTSD
J Clin Psychopharmacol. 2006 Apr;26(2):152-6.
Reboxetine versus fluvoxamine in the treatment of motor vehicle accident-related posttraumatic stress disorder: a double-blind, fixed-dosage, controlled trial.
Spivak B, Strous RD, Shaked G, Shabash E, Kotler M, Weizman A. Ness-Ziona Mental Health Center, Ness-Ziona, Israel. spivakb@post.tau.ac.il
BACKGROUND: Motor vehicle accidents (MVAs) are a leading cause of posttraumatic stress disorder (PTSD) in the general population. Alterations in norepinephrine and serotonin systems have been proposed as mechanisms involved in the pathophysiology of the condition, with treatment directed at these neurotransmitter systems. Reboxetine, a selective norepinephrine reuptake inhibitor, exhibits high affinity and selectivity for the human norepinephrine transporter. Inasmuch as PTSD may be associated with dysregulation of noradrenergic activity, the present double-blind randomized clinical trial intended to evaluate reboxetine's efficacy in the management of MVA-related PTSD and to compare its efficacy with a medication commonly used in PTSD, the selective serotonin reuptake inhibitor fluvoxamine. METHODS: Forty patients with MVA-related PTSD attending a local community mental health outpatient clinic were randomized to receive a fixed dose of either reboxetine (8 mg/d) or fluvoxamine (150 mg/d) in a double-blind fashion for a period of 8 weeks. RESULTS: At baseline and at study end point, the 2 subgroups demonstrated no statistical differences in scores on PTSD, depression, and anxiety rating scales. Both medications led to significant improvements in all clinical scales measured. Nine patients receiving reboxetine and 3 receiving fluvoxamine withdrew from the study because of side effects. CONCLUSIONS: Study observations indicate comparable efficacy of reboxetine and fluvoxamine in the management of MVA-related PTSD despite reboxetine's selective noradrenergic activity. Reboxetine appears to be at least as effective as fluvoxamine and may offer an alternative management option in this often difficult-to-treat and disabling condition. A lower and flexible reboxetine dosing schedule will be recommended for future research to improve its tolerability in PTSD patients.
Prog Neuropsychopharmacol Biol Psychiatry. 2006 Sep 30;30(7):1353-5. Epub 2006 Apr 24.
Monotherapy with reboxetine in amphetamine withdrawal syndrome.
Molina JD, de Pablo S, López-Muñoz F, Alamo C, Blasco-Fontecilla H, González-Parra S. Acute Inpatients Unit, Doctor Rodríguez Lafora Psychiatric Hospital, Carretera de Colmenar Viejo, Km. 13.800, Madrid 28049, Spain. candrader@medynet.com candrader@medynet.com
Amphetamine withdrawal can induce a condition with the symptoms of major depression. We report the case of a 46-year-old woman with antecedents of abuse of amphetamines and amphetamine derivatives from age 16 to age 41, who in the 5 years since withdrawal presented recurrent depression resistant to treatment. She was treated with maximum doses of selective serotonin reuptake inhibitors and lithium, but there was no remission of symptoms. On being treated with reboxetine, a selective noradrenaline reuptake inhibitor, euthymia was achieved, without negative after effects. Several studies have shown that noradrenaline plays an important role in the modulation of the response to amphetamines. The findings in this case suggest that reboxetine may constitute an interesting alternative for the treatment of amphetamine withdrawal syndrome (AWS).
Reboxetine In LSD-induced Hallucinogen Persisting Perception Disorder
Isr J Psychiatry Relat Sci. 2002;39(2):100-3.
LSD-induced Hallucinogen Persisting Perception Disorder with depressive features treated with reboxetine: case report.
Lerner AG, Shufman E, Kodesh A, Kretzmer G, Sigal M. Lev Hasharon Mental Health Medical Center, Pardessya, POB 90000, Netanya, 42100, Israel. lerneram@internet-zahav.net
We would like to present the case of a patient who had a prior history of cannabis, ecstasy (MDMA) and LSD abuse and who developed both Hallucinogen Persisting Perception Disorder (HPPD) and a major depressive episode. Following two unsuccessful SSRIs trials, reboxetine was prescribed. During a six-month follow-up period on reboxetine 6 mg./day, no exacerbation of the visual disturbance or recurrence of the depressive features were reported. Reboxetine may have an alpha 2 adrenoreceptor modulating effect on both noradrenaline and serotonin release, thus reboxetine's alpha 2 adrenoreceptor modulating effect on noradrenaline release may affect sympathetic activity and be involved in the recovery process.
Reboxetine In Bulimia Nervosa
J Psychopharmacol. 2004 Sep;18(3):423-8.
Use of reboxetine in bulimia nervosa: a pilot study.
Fassino S, Daga GA, Boggio S, Garzaro L, Pierò A. Department of Neurosciences, Section of Psychiatry, University of Turin, Turin, Italy. secondo.fassino@unito.it
The pharmacological approach to bulimia nervosa is mainly based (BN) on selective serotonin reuptake inhibitors, but many elements suggest the possible involvement of the noradrenergic system in this disorder. The aim of the study was to assess the efficacy of reboxetine--a selective norepinephrine uptake inhibitor--in a sample of bulimic outpatients, after 3 months of treatment. Twenty-eight of 77 consecutively admitted patients with a DSM-IV diagnosis of BN (without Axis I comorbidity) received reboxetine. All patients were assessed at baseline (T0), and after 1 month (T1) and 3 months (T3), respectively, of treatment with reboxetine 4 mg/day. The subjects were administered the following questionnaires: Hamilton Rating Scale for Anxiety (HAM-A) and for Depression (HAM-D), Global Assessment Functioning (GAF), Eating Disorder Inventory-2 (EDI-2) and Body Shape Questionnaire (BSQ). Sixty percent of the patients were responsive to treatment(evaluated as a 50% decrease of bulimic behaviours). After 3 months of treatment, a significant reduction emerged in the scores of various EDI-2 subscales (Bulimia, Drive for Thinness, Body Dissatisfaction, Social Insecurity, Interpersonal Distrust, etc.) and in the BSQ total score. Moreover, depressive symptoms (HAM-D) and Global Functioning (GAF) scores showed a significant improvement. These data support a fast and favourable effect of reboxetine in the treatment of BN, both on symptoms and psychopathological features. Moreover, the specific and strong action of reboxetine on improvement of social functioning is also supported in this disorder.
Reboxetine In Cocaine Dependence Disorder
Hum Psychopharmacol. 2005 Apr;20(3):189-92.
Reboxetine for the treatment of patients with Cocaine Dependence Disorder.
Szerman N, Peris L, Mesías B, Colis P, Rosa J, Prieto A; Grupo de Estudio del Uso de Reboxetina en Dependencia a Cocaina. Moratalaz Mental Health Department, Madrid, Spain.
BACKGROUND: Although several approaches have been attempted for cocaine dependence, the pharmacological treatment of this serious disorder remains unclear. To date, desipramine, a tricyclic antidepressant of great noradrenergic activity, has shown the best results. Reboxetine, a selective noradrenaline reuptake inhibitor, might be an effective therapeutic option for this severe drug addiction. The aim was preliminarily to assess reboxetine in a group of cocaine dependent patients, selected from The Madrid City Council Drug Addiction Program primary care centres. METHOD: 26 patients with a diagnosis of cocaine dependence disorder (DSM-IV 304.20) were selected to receive open treatment with reboxetine, 8 mg/day, for 12 weeks. Follow up assessments comprised cocaine consumption, treatment retention rate and change in standard structured psychometric instrument scores: cocaine selective severity assessment, Hamilton anxiety scale, Hamilton depression scale and clinical global impression, throughout the treatment period. RESULTS: Data were obtained from 20 patients; 10 of them remained abstinent, whereas the other 10 consumed cocaine at some time during the study. The treatment retention rate at week 12 was 61.5%. The psychometric instrument mean scores showed marked decreases throughout the treatment period. CONCLUSION: Reboxetine might be an effective and safe therapeutic option for cocaine dependence disorder. The aversive effects, as well as the high blockage reported by some patients consuming cocaine during the trial, might be related to treatment. If confirmed in large clinical trials, the trends suggested by this study would confirm the role of noradrenergic function in the treatment of cocaine dependence.
Reboxetine In Hyperkinetic Conduct Disorder
J Child Adolesc Psychopharmacol. 2005 Apr;15(2):259-69.
Reboxetine as an optional treatment for hyperkinetic conduct disorder: a prospective open-label trial.
Mozes T, Meiri G, Ben-Amity G, Sabbagh M, Weizman A. Ness-Ziona Mental Health Center, Children Psychiatric Department, Ness-Ziona, Israel. tmoses@post.tau.ac.il
BACKGROUND AND PURPOSE: Hyperkinetic conduct disorder (HCD) has been identified as a common psychiatric diagnosis among children and adolescents. This disorder affects many life aspects of both child and family. The aim of this study was to examine the efficacy of the selective norepinephrine reuptake inhibitor (SNRI), reboxetine, in treating children with HCD and its influence on associated symptoms, such as aggressiveness, impulsivity, anxiety, and depression. METHODS: Fifteen children, 5-14 years of age, diagnosed with HCD, participated in a 12- week, prospective, open-label trial with reboxetine (4-8 mg/d). They were examined for changes in: ADHD symptoms, as measured by the Conners Abbreviated (10-item) Teacher Rating Scale, aggression, as measured by the Yudofsky Overt Aggression Scale (OAS), impulsivity, as measured by the Plutchik impulsivity scale (IS), anxiety, as measured by the Revised Children's Manifest Anxiety Scale (RCMAS), and depressive mood, as measured by the Hamilton Rating Scale for Depression (HAM-D). RESULTS: There was a significant symptomatic improvement for HCD symptoms and associated symptoms. CONCLUSION: Our findings suggest that reboxetine may be effective in the treatment of HCD and associated symptoms
Reboxetine vs Venlafaxine XR In Major Depression and major depression with anxiety features
Hum Psychopharmacol. 2006 Jul;21(5):337-45.
Comparison of efficacy and tolerability of reboxetine and venlafaxine XR in major depression and major depression with anxiety features: an open label study.
Akkaya C, Sivrioglu EY, Akgoz S, Eker SS, Kirli S. Psychiatry Department, Uludag University, Medical Faculty, Bursa, Turkey.
OBJECTIVE: The aim of this study was to compare the efficacy and tolerability of reboxetine in the treatment of major depressive disorder (MDD) and MDD with anxiety features to venlafaxine XR. METHOD: Patients with MDD, aging 18 between 65 years, were randomly allocated to two groups receiving either open-label venlafaxine XR capsules (n = 50) or reboxetine tablets (n = 43). Subjects were administered Hamilton Depression Rating Scale (HAM-D) and Hamilton Anxiety Scale (HAM-A) at baseline and 2, 4, 7, 10 weeks after the baseline visit. RESULTS: Response rates to antidepressant treatment were significantly higher in the venlafaxine XR group at 10th week. When patients having anxious depression were analysed separately; response rate for anxiety of reboxetine group was significantly higher at 7th week only. Mean number of side effects were significantly higher in reboxetine group. Only one subject in each group was dropped out due to side effect. CONCLUSION: We may suggest that reboxetine is as effective and tolerable as venlafaxine XR in the treatment of MDD and MDD with anxiety features, and it may be considered a treatment option to venlafaxine XR.
Reboxetine vs Sertraline In MDD
Turk Psikiyatri Derg. 2005 Fall;16(3):153-63.
[Comparison of reboxetine and sertraline in terms of efficacy and safety in major depressive disorder][Article in Turkish]
Eker SS, Akkaya C, Akgöz S, Sarandöl A, Kirli S. Uludað U Tip Fak., Bursa.
OBJECTIVE: To compare the efficacy, safety and tolerability of reboxetine and sertraline in major depressive disorder (MDD). METHOD: The study subjects consisted of 41 patients who met the DSM-IV MDD diagnostic criteria. Patients were randomly assigned to receive either reboxetine or sertraline. During the study the patients were assessed 6 times (baseline visit=day 0, visit 1=day 8, visit 2=day 22, visit 3=day 36, visit 4=day 57 and visit 5=day 78) over 11 weeks. Antidepressant response was measured by the Hamilton Depression Rating Scale (HDRS), Clinical Global Impressions-Severity of Illness (CGI-SI) and Global Impressions-Global Improvement (CGI-GI). RESULTS: Comparing the two groups in terms of response and remission (HAM-D< or =10) measures, the results were in favour of the reboxetine group at visits 2, 3 and 4. At visit 5, the scores were similar and no statistically significant difference was found between the two groups. However, when remission was evaluated as HAM-D< or =7, a significant statistical difference was found in favour of the reboxetine group. Evaluating the side effects, dry mouth, sweating, palpitation, headache, hot flushing and sedation were more frequent in the reboxetine group. Only one patient, in the reboxetine group, dropped out due to a side effect (constipation). CONCLUSION: Higher rates of full remission achievement, which is the main target of MDD treatment, in the reboxetine group compared with the sertraline group may be due to the suppression of anxiety symptoms by the noradrenergic feature of the drug. In order to understand the role of the noradrenergic system in treating MDD, larger patient samples are needed. Both reboxetine and sertraline were well tolerated and effective in treating MDD.
Reboxetine In ADHD
J Am Acad Child Adolesc Psychiatry. 2005 May;44(5):428-33.
Six-week open-label reboxetine treatment in children and adolescents with attention-deficit/hyperactivity disorder.
Ratner S, Laor N, Bronstein Y, Weizman A, Toren P. Tel Aviv-Brull Community Mental Health Center, Israel.
OBJECTIVE: This open-label study assessed the effectiveness of reboxetine, a selective norepinephrine reuptake inhibitor, in children and adolescents with attention-deficit/hyperactivity disorder (ADHD) resistant to a previous methylphenidate trial. METHOD: Thirty-one child and adolescent outpatients, aged 8 to 18 (mean age, 11.7; SD = 2.87) years, diagnosed with ADHD were enrolled in a 6-week open-label study. Assessments included rater-administered scales (DSM-IV ADHD Scale; Clinical Global Impressions Scale), parent-administered scales (the Abbreviated Conners Rating Scale), and self-administered-scales for the evaluation of depressive (Children's Depression Inventory) and anxiety (the Revised Children's Manifest Anxiety Scale) symptoms. Reboxetine was initiated and maintained at a dose of 4 mg/day. RESULTS: A significant decrease in ADHD symptoms, on all scales measured, was noted. Adverse effects were relatively mild and transient. The most common adverse effects were drowsiness/sedation and gastrointestinal complaints. CONCLUSIONS: The results of the current open-label study suggest the effectiveness of reboxetine in the treatment of ADHD in methylphenidate-resistant children and adolescents. Double-blind, placebo-, and active comparator-controlled studies are indicated to rigorously test the efficacy of reboxetine in ADHD.
J Child Adolesc Psychopharmacol. 2006 Dec;16(6):803-4.
Reboxetine use in the treatment of attention-deficit/hyperactivity disorder.
Cak HT, Cetin FC.
