Tapering antidepressants: is 3 months slow enough?

Background

Antidepressants are used by 10% of the US population. Amongst these users, most will stop their antidepressant at some point, and about half - over a million people - will experience withdrawal effects, given usual taper rates. Moreover, recent data suggest that relapse rates (in patients with depression, panic disorder, or bipolar disorder) are higher with shorter tapers. How long is long enough? Recent data from narcolepsy research suggest that the physiologic processes associated with antidepressant discontinuation last over three months.

Recent results

Antidepressants have long been used in control of narcolepsy with cataplexy, but their sustained efficacy in this role has been in question. Thus prior to a trial of a new medication for cataplexy, antidepressants were carefully tapered and cataplexy rates monitored. Patients who had never received antidepressants were used as controls. Antidepressant discontinuation was associated with a dramatic increase in cataplexy rates, as anticipated; but importantly, these rates did not normalize, relative to the never-exposed patients, for over 3 months.

Conclusion

These cataplexy data suggest that common antidepressant taper rates may be far too brief. Patients who are doing well and ready to discontinue their antidepressant might experience fewer withdrawal effects and fewer relapses with rates much longer than those now routinely used.     

Reviewing long-term antidepressants can reduce drug burden: a prospective observational cohort study

Background

Antidepressant prescribing continues to rise. Contributing factors are increased long-term prescribing and possibly the use of higher selective serotonin re-uptake inhibitor (SSRI) doses.

Aim

To review general practice patients prescribed the same antidepressant long-term (≥2 years) and evaluate prescribing and management pre and post-review.

Design and setting

Prospective observational cohort study using routine data from 78 urban general practices, Scotland.

Method

All patients prescribed antidepressants (excluding amitriptyline) for ≥2 years were identified from records November 2009 to March 2010. GPs selected patients for face-to-face review of clinical condition and medication, December 2009 to September 2010. Pre- and post-review data were collected; average antidepressant doses and changes in prescribed daily doses were calculated. Onward referral to support services was recorded.

Results

8.6% (33 312/388 656) of all registered patients were prescribed an antidepressant, 47.1% (15 689) were defined as long-term users and 2849 (18.2%) were reviewed. 811 (28.5%) patients reviewed had a change in antidepressant therapy: 7.0% stopped, 12.8% reduced dose, 5.3% increased dose, and 3.4% changed antidepressant, resulting in 9.5% (95% CI = 9.1% to 9.8% P<0.001) reduction in prescribed daily dose and 8.1% reduction in prescribing costs. 6.3% were referred onwards, half to NHS Mental Health Services. Pre-review SSRI doses were 10–30% higher than previously reported.

Conclusion

Almost half of all people prescribed antidepressants were long-term users. Appropriate reductions in prescribing can be achieved by reviewing patients. Higher SSRI doses may be contributing to current antidepressant growth.     

What are older peoples' experiences of taking antidepressants?

Background: Antidepressants are prescribed widely to older people but little is known about older peoples’ own reported experiences of taking them in routine practice. Methods: A doctor interviewed 92 people, aged over 65, with a hospital diagnosis of depression, who had been prescribed an antidepressant in the past year. Results: Most of the subjects were prescribed a selective serotonin reuptake inhibitor (SSRI), at a standard dose, for at least 8 weeks. Most people felt the antidepressants were helpful, although a third felt they made no difference. Two thirds of older people reported having adverse effects of which most were moderate or severe. The most common adverse effects were headache and dry mouth. Only a third said that they always took their tablets. Limitations: The sample was restricted to older people seen by hospital services. Interviews were carried out by a doctor and patients may not have been entirely truthful. Conclusions: Older people have important views about their treatment that they are prepared to tell a doctor. A lot of older people do not think their antidepressants are helpful, and the majority experience adverse effects. Many do not always take their medication. Doctors should routinely ask older people about their experiences of taking antidepressants.     

Temperament and character inventory dimensions as a predictor of response to antidepressant treatment in major depression

BACKGROUND: Cloninger's theory of personality, including 4 temperament dimensions and 3 character dimensions, is one of the most noteworthy theories in recent years. Several studies have explored temperament dimensions as a predictor of response to antidepressant treatments in major depression, but these have provided inconsistent results. The present study explored temperament as well as character dimensions, as measured by the Temperament and Character Inventory (TCI), as possible predictors of response to maprotiline, the most-widely prescribed antidepressant in Japan. METHODS: 86 consecutive patients with major depression underwent a 16-week open trial of maprotiline. They filled out the TCI at baseline, and were followed up at weeks 8 and 16 by using the Hamilton Rating Scale for Depression. RESULTS: Hierarchial logistic regression analyses demonstrated that response to maprotiline was significantly predicted by the cooperativeness score at the 8-week outcome assessment, and by the self-directedness score at the 16-week outcome assessment, after controlling the possible effects of clinical variables on the response. There was no evidence that either temperament dimensions or their 2-way interactions significantly predicted the response. LIMITATIONS: Large replication studies with other antidepressants are needed for generalizing the results in this study. CONCLUSIONS: The results in this study regarding temperament dimensions seem consistent with findings in previous studies, which are, as a whole, inconsistent with each other. It is suggested that character dimensions (particularly cooperativeness and self-directedness), rather than temperament dimensions, may be important predictors of response to antidepressants. Antidepressants may differ in the personality configurations that predict optimal responses.     

Deltamethrin, a pyrethroid insecticide, could be a potential antidepressant agent

Antidepressants, including tricyclic antidepressants, monoamine oxidase inhibitors, selective serotonin reuptake inhibitors and serotonin-noradrenalin reuptake inhibitors, are the main biological treatment for major depression. However, not all depressed patients improve clinically despite appropriate treatment. Thus, the exploration of novel antidepressants with novel mechanisms of action may help to develop more effective agents. Deltamethrin is a pyrethroid insecticide that is a widely used and has a low acute toxicity in mammals. Recent studies in vivo and in vitro have shown that the inducible effect of deltamethrin on brain-derived neurotrophic factor (BDNF) gene expression is very potent and tends to be sustained. With recent evidence that the activation of the BDNF-dependent pathway plays an important role in the mechanism of antidepressant therapeutic action, deltamethrin or derivatives thereof could have potential antidepressant therapeutic effects. Further evaluation of the therapeutic and toxic effects of this drug in animal models is needed before clinical trials can begin.