CLICK HERE TO RETURN TO THE MAIN ANALYSIS AND REVIEW OF
| Ref | SIGNIFICANT REFERENCES TO ‘EVIDENCE’ AND THE LACK OF IT |
| 4 | The conclusions of the Group and the evidence on which they are based are set out in the report. Inevitably, they represent a snap shot in time, based on the evidence available to the Group during the course of its work. |
| 5 | As Chairman of the Expert Group, I am indebted to all the members of the Group. Their commitment has been unstinting and their resolve, carefully and painstakingly to look at all the evidence available, utterly determined. |
| 7 | From these analyses, the Group concluded that there is no clear evidence of an increased risk of self-harm and suicidal thoughts in young adults of 18 years or over. |
| 7 | There is epidemiological evidence that the risk of self-harm in depressed patients is greatest around the time of presentation to medical services. |
| 7 | There is insufficient evidence from clinical trial data to conclude that there is any marked difference between members of the class of SSRIs, or between SSRIs and other antidepressants, with respect to their influence on suicidal behaviour. |
| 8 | Evidence from non-experimental studies based on the General Practice Research Database indicatesthat there is no increased riskof suicidal behaviour with SSRIs compared with tricyclic antidepressants. |
| 8 | There is no clear evidence that there is an increased risk of self-harm or suicidal thoughts when SSRIs are discontinued. |
| 8 | Evidence of a relationship between suicidal behaviour and increasing/decreasing dose is not robust; however, patients should be monitored around the time of dose changes for any new symptoms or worsening of disease. |
| 8 | There is evidence that withdrawal reactions are less severe when the dose is tapered gradually over a period of several weeks, according to the patient’s need. |
| 8 | There is no clear evidence that the SSRIs and related antidepressants have a significant dependence liability or show development of a dependence syndrome according to internationally accepted criteria |
| 8 | Upon review, the Group considered that there was no evidence from clinical trials that increasing the dose above that recommended increases efficacy in the treatment of depressive illness. |
| 8/9 | This review, combined with evidence from usage databases that a proportion of patients were being started on paroxetine at doses higher than those recommended, led CSM to advise that a reminder of the recommended dose of paroxetine should be sent to health professionals. |
| 9 | In the absence of evidence of a benefit from increasing the dose, good practice would be to maintain patients on the lowest efficacious dose. |
| 21 | the evidence was not sufficient to confirm a causal association between SSRIs and suicidal behaviour, although an effect in a small high-risk population could not be ruled out … |
| 22 | The conclusions of this meeting were that the evidence presented did not justify a change to the regulatory position … |
| 27 | Rigorous evidence for the efficacy of treatment of depressive illness in children and adolescents has been lacking. |
| 31 | Some authors have suggested that increased prescribing of antidepressants in recent years, possibly indicating improved detection and management of depression, may have led to reductions in suicide rates in some countries. Evidence for this is controversial, and some have expressed concerns that antidepressants may, in fact, precipitate suicidal behaviour in some individuals. |
| 46 | There is emerging evidence that the risk of adverse drug reactions may be related to specific genotypes. There should be further research into the pharmacogenetic determinants of efficacy and toxicity associated with SSRIs. |
| 50/1 | Following previous consideration of the paediatric data for fluoxetine, the Paediatric Medicines Working Group of the CSM had considered that the evidence for efficacy was robust for short-term use in major depressive disorder. |
| 52 (2) | Efficacy (in major depressive disorder) was evaluated in two randomised, double-blind clinical trials involving a total of 407 patients treated for eight or 12 weeks. A total of 210 patients received citalopram. Dose range was 20mg-40mg/day. One involving 174 children and adolescents aged seven to 17 years provided some evidence of efficacy. No evidence of efficacy was found in the other trial involving 244 adolescents (13-18 years). |
| 54 | There was little evidence that fluoxetine alone was different to placebo or that CBT alone was different to placebo. |
| 60 | There was no strong evidence of a difference in risk between the drugs for non-fatal suicidal behaviour. |
| 60 | The results are presented in Table 6.6 and show evidence of an increased risk for both fluoxetine and paroxetine compared to amitriptyline which reaches the conventional level of statistical significance despite the small numbers of young people in the study. |
| 60 | Although the overall results show no strong evidence of an increased risk of suicidal events in young people exposed to either fluoxetine or paroxetine compared to dothiepin, the strongest odds ratios were in relation to paroxetine (table 6.6). |
| 61 | There was evidence of an increased risk of non-fatal self-harm for current SSRI use compared to current TCA use amongst those aged =18 years, which may be highest for those prescribed paroxetine compared to other SSRIs. |
| 63/64 | There was weak evidence of an elevated risk of suicidal behaviour associated with paroxetine use relative to other SSRIs (OR = 1.4 95% CI 0.9 – 2.2). |
| 64 | Among those under 19 years, there was no evidence of a relationship between suicidal behaviour risk, duration of therapy and SSRI use relative to non-SSRI use. |
| 64 (2) | Whilst there was evidence of an increased risk with different durations of exposure to SSRIs, there was no evidence of a trend in risk with increasing duration of use… |
| 64 | There was some evidence of a trend of increasing risk associated with increasing duration of therapy with paroxetine relative to other SSRI use … |
| 64 (2) | There was some evidence that this increased risk may differ by duration of SSRI use and paroxetine use among children, but there was no clear evidence of an association with increasing duration of use. |
| 65 (2) | The study reinforces evidence from other GPRD studies about the increased risk of suicidal behaviour in adolescents exposed to SSRIs compared to non-SSRIs. This increased risk is present at all time points considered. The OR estimates are variable, but there is no evidence of a trend associated with increasing duration of therapy. |
| 65 (2) | There is some evidence of a trend in risk associated with increasing duration of paroxetine therapy compared to other SSRIs in adolescents, although all the confidence intervals overlap and there is no evidence that any differ from one. |
| 65 (3) | These three GPRD studies contain overlapping sets of patients, but have employed different study designs. The results between the three studies are entirely consistent with each other. Overall there is evidence that children and young people exposed to SSRIs are at increased risk of suicidal behaviour compared to those exposed to other antidepressants. Furthermore, there is also consistent evidence from all three studies that children and young people exposed to paroxetine may be at increased risk of suicidal behaviour compared to those exposed to other SSRIs. It is possible that these results are due to confounding by indication where patients thought to be at greater risk of suicidal behaviour are preferentially treated with SSRIs due to their relative lack of toxicity in overdose. There is also some evidence from the GSK study that adolescents prescribed paroxetine may be more likely to have a previous history of suicidal behaviour than patients prescribed other SSRIs. The analyses controlled for previous history, however it remains possible that residual confounding may have contributed to the result. |
| 66 (4) | Although evidence-based medicine relies on the availability of high quality trial evidence, it was acknowledged that doctors often have to make treatment decisions in the absence of such conclusive evidence and will, particularly in specialist settings, prescribe medicines that have not been licensed for a particular use. Therefore, the law allows doctors freedom to prescribe in the contraindicated population if they consider, from their knowledge and experience, it to be in the best interests of the patient. It remains possible that SSRIs and the related antidepressants may be effective in the treatment of depressive illness in some children, but the currently available evidence does not identify the population which may benefit. |
| 72 | Disentangling the evidence using published data alone is problematic as much research in this area is sponsored by the pharmaceutical industry. |
| 74 | A meta-analysis of data for fluoxetine (an SSRI) found no evidence that suicidal acts were less frequent amongst adults receiving active treatment: their pooled incidence was fluoxetine: 0.3%, placebo: 0.2% and TCAs: 0.4% |
| 74 | Suicide is rare, even amongst people with depression. Thus, due to power limitations, the lack of clear clinical trial evidence of the effect of antidepressants on suicide is not surprising. |
| 75 (2) | In addition, it has been suggested that response to treatment may lead to ‘reactivation’ amongst those whose depression previously prevented them from acting on suicidal impulses. There is no published epidemiological evidence that provides clear evidence of this phenomenon. |
| 75 (2) | Reassuringly, time-trends for suicide (England and Wales) and non-fatal self-harm (Oxford, UK) in children and adolescents – the groups in whom the risks of SSRIs have been demonstrated – provide no consistent evidence of adverse trends paralleling increased prescribing in the 1990s, although there is some recent evidence of a rise in self-harm in young females |
| 76 | In the absence of clear evidence from clinical trials, researchers have investigated whether rises in antidepressant prescribing are associated with reductions in suicide at a population level… |
| 78 | There are a number of limitations to the use of randomised controlled trial evidence in determining the effect of SSRIs on suicide risk. |
| 86 | Heterogeneity tests showed no evidence of heterogeneity between studies, and the results from fixed and random effects models were identical in most cases. |
| 87 | Overall, there is no strong evidence of an increased risk of suicidal events for adult patients with depression exposed to paroxetine compared to placebo, although the point estimates and confidence intervals are consistent with a possible increase in risk. |
| 87 | Overall, these data show no conclusive evidence that adult patients exposed to paroxetine are at increased risk of suicidal events compared with patients exposed to either placebo or another active drug in any of the indications investigated. |
| 87 | The available data on the risk of suicidal behaviour in young adults do not provide clear evidence of an increased risk in this age group. Due to differences in maturity we cannot rule out the possibility that some young adults may have a risk of suicidal behaviour similar to that seen in children and adolescents. |
| 88 | Whilst the results provide no clear evidence of an increased risk, the range of risk ratios included within the 95% confidence intervals are consistent with the possibility of a small increased risk of suicidal events for patients exposed to paroxetine compared with those exposed to placebo, but not paroxetine compared with other antidepressants. The confidence intervals are, however, also consistent with a small protective effect in relation to suicidal events. |
| 94/95 | In the TCA-controlled trials there was evidence of a difference between genders in the incidence of worsening suicidal thoughts which was higher in females on fluoxetine (incidence difference =3%). |
| 96 | Despite small numbers in the age groups, it appears that the increased risk on fluvoxamine was consistent across all age groups (including the 18-29 year olds), with no evidence that it was heightened in young adults. |
| 99 | There was, however, strong evidence that placebo patients without suicidal thoughts at baseline had more suicidal thoughts on study than those on sertraline (p=0.01). |
| 102 | However, in the 18-29 age group there is some evidence of a slight increase in the risk of any suicide-related event on venlafaxine IR compared to placebo or venlafaxine ER. |
| 103 | In relation to dose, the analysis showed evidence of a trend (p<0.02) for both worsening and emergence of suicidal thoughts, with fewer events in patients receiving the higher doses (Tables 7.34 and 7.35). |
| 105 | There was no strong evidence of a difference in risk between the drugs for either fatal or non-fatal suicidal behaviour, either overall or stratified by age. |
| 107 | The overall adjusted odds ratio (OR) of non-fatal self-harm was 1.0 (95% CI 0.9 - 1.1), and of suicide was 0.6 (95% CI 0.3 - 1.3) in SSRI users compared with TCA users, with little evidence that associations differed between drugs over time since starting or stopping treatment. |
| 107 (2) | There was evidence that risks of non-fatal self-harm in SSRI users compared with TCA users differed by age group; the adjusted OR of non-fatal self-harm for SSRI users compared with TCA users for those =18 years was 1.6 (95% CI: 1.0-2.5). No association was apparent in other age-groups (Table 7.38), although there was weak evidence of a lower risk in SSRI users compared with TCA users in those over 30 years of age. |
| 108 | There was no overall evidence of an increased risk of suicide in patients exposed to SSRIs compared with TCAs (OR= 0.6 (0.3-1.3)). |
| 109 | There was no evidence that event rates among adults were elevated in SSRI users compared to non-SSRI users |
| 109 | Among adults, there was weak evidence that the risk of suicidal behaviour was lower in SSRI users relative to non-SSRI users (OR=0.8, 95%CI=0.7-1.0), and was not significantly different with paroxetine relative to other SSRI use (OR=1.1, 95%CI=0.9-1.3). |
| 109 (2) | There was no evidence of a relationship between suicidal behaviour risk, duration of therapy and SSRI use. There was also no evidence among adults of a trend of increased suicidal behaviour among SSRI users relative to non-SSRI users with increasing duration of therapy. |
| 110 | Although the overall results show no strong evidence of an increased risk of suicidal events in adults exposed to either fluoxetine or paroxetine compared to dothiepin, the strongest odds ratios were in relation to paroxetine (table 7.36). |
| 110 | In common with the other studies, there is no evidence of an increased risk of suicidal behaviour in adults exposed to SSRIs compared to non-SSRIs or for paroxetine compared to other SSRIs. |
| 110 (3) | The findings of the three studies are broadly consistent with each other. Overall, there is no evidence of an increased risk of suicidal behaviour in adults exposed to SSRIs compared to a range of other anti-depressants. However, there is evidence that children and young people exposed to SSRIs are at increased risk of suicidal behaviour compared to those exposed to other anti-depressants. Furthermore, there is also consistent evidence from all three studies that children and young people exposed to paroxetine may be at increased risk of suicidal behaviour compared to those exposed to other SSRIs. |
| 117 | There is evidence that the risk of suicidal behaviour is highest around the time of presentation to medical services and starting treatment, possibly because the disease is at its worst before a patient will seek medical help. |
| 117 | There is insufficient evidence from clinical trial data to conclude that there is any marked difference between members of the class of SSRIs, or between SSRIs and other antidepressants, with respect to their influence on suicidal behaviour. |
| 118 | The evidence from the GPRD studies of the lack of any difference between the risk of suicidal behaviour with SSRIs compared with TCAs, supports a general antidepressant effect rather than an SSRI-specific effect. |
| 118 | The clinical trial data in children raise a concern that in some young adults there may also be a negative balance of risks and benefits for SSRIs. There is no clear evidence of this from the adult data considered – from clinical trials or from the GPRD studies. |
| 118 | There is epidemiological evidence that the risk of self-harm in depressed patients is greatest around the time of presentation to medical services. |
| 119 | There is insufficient evidence from clinical trial data to conclude that there is any marked difference between members of the class of SSRIs, or between SSRIs and active comparators, with respect to their influence on suicidal behaviour. |
| 119 | Evidence from non-experimental studies based on the General Practice Research Database indicates that in adults there is no increased risk of suicidal behaviour with SSRIs compared with TCAs. |
| 119 | There is no clear evidence of an increased risk of self-harm and suicidal thoughts in young adults of 18 years or over. |
| 119 | There is no clear evidence that there is an increased risk of self-harm or suicidal thoughts when SSRIs are discontinued. |
| 119 | Evidence of a relationship between suicidal behaviour and increasing/decreasing dose is not robust; however patients should be monitored around the time of dose changes for any new symptoms or worsening of disease. |
| 123 | There are a number of limitations to the use of randomised controlled trial evidence in determining the risk of withdrawal reactions in association with the SSRIs and related antidepressants. |
| 128 (2) | There was no evidence of any difference between the citalopram and placebo groups in the severity and frequency of any individual adverse event. The authors state that there was no evidence of withdrawal reactions to citalopram in the study. |
| 132 | The frequency of withdrawal symptoms following abrupt and gradual withdrawal of paroxetine suggests that gradual reduction reduces their frequency. Furthermore, where the incidence of withdrawal reactions in relation to the patients’ dose of paroxetine has been examined, there is evidence to suggest the incidence of withdrawal reactions is higher in people taking higher doses (Table 8.5 below). |
| 133 | There is evidence from the escitalopram studies that patients are at an increased risk of withdrawal reactions following longer-term treatment (see section below). |
| 135 | As can be seen from Table 8.8 below, these data do not provide strong evidence to suggest that the risk of adverse events upon withdrawal increases following longer duration of treatment. |
| 151 (5) | With reference to ICD 10 criteria, SSRIs do not appear to lead to craving in comparison with other drugs of dependence such as opiates, heroin, cocaine and alcohol (criterion 1). There is no clear evidence of impaired control (criterion 2) apart from isolated single case studies in individuals who misuse other substances. There is clear evidence of withdrawal symptoms on discontinuation of SSRIs (criterion 3); also some patients take care not to run out of the drug, possibly to avoid withdrawal symptoms (criterion 3). However, this is not nearly as marked as in typical drugs of dependence. Tolerance does not appear to be significant compared with other drugs such as benzodiazepines (criterion 4). There is some evidence of preoccupation, or rather patients making sure they have a supply of SSRI drugs (criterion 5), but this does not appear to be prominent and may be more a feature of withdrawal avoidance. Finally, there does not appear to be evidence of persistence despite harmful consequences, partly perhaps because the harmful consequences related to SSRI use are relatively minor, and the benefits to the individual greater, compared with other typical dependence-producing drugs (criterion 6). So although SSRIs meet two out of the six ICD 10 criteria (numbers 3 and 5), the evidence for criterion 5 is limited compared with other typical drugs of dependence. |
| 151 | Overall, in relation to DSM IV there is evidence that three out of the seven criteria are sometimes met. However, the extent to which SSRIs meet these criteria is much less than with other typically dependence-producing drugs. |
| 152 (2) | However, withdrawal reactions alone are not sufficient reinforcers of continued drug use in general terms, and in SSRIs in particular, on the basis of the current evidence. The SSRIs do not have an equivalent dependence potential to benzodiazepines on the basis of the existing evidence, although they both produce characteristic withdrawal reactions following chronic exposure. |
| 152 | A review of the available published and unpublished data revealed no evidence that these drugs were associated with dependence, and the results of clinical and pre-clinical studies indicate that dependence, and the abuse potential of these drugs, is low. |
| 155 (2) | There is increasing evidence from clinical studies, published case reports and spontaneous reports to suggest that maternal use of SSRIs and related antidepressants, particularly during the third trimester, may lead to neonatal withdrawal reactions. The most convincing evidence is that for paroxetine. |
| 156 (2) | The SSRIs have been associated with a large number of spontaneous reports of withdrawal reactions. However, review of these reports and the published literature do not provide clear evidence that the SSRIs and related antidepressants have a significant dependence liability or show development of a dependence syndrome by meeting the criteria for either DSM-IV or ICD-10. Furthermore, although there are isolated reports of the abuse of fluoxetine and sertraline by known drug abusers, these comprise a very small number in relation to the usage of these drugs. In this review no evidence has been identified to suggest that abuse of SSRIs occurs in patients without a prior history of substance abuse. |
| 156 (2) | In contrast, benzodiazepines have been clearly established as drugs which may produce dependence and withdrawal reactions. Current evidence does not support the view that SSRIs and related antidepressants have a comparable dependence. This is not to mimimise the distress that individuals may experience as a result of SSRI withdrawal reactions, which can in some cases be disturbing or disabling to the individual; rather the existence of withdrawal reactions alone is not sufficient to support the existence of an SSRI dependence syndrome or to provide evidence of dependence potential. |
| 156 | The available evidence shows that on discontinuation of treatment, gradual tapering of the dose of SSRI over several weeks or months significantly reduces the frequency and severity of withdrawal reactions. |
| 156 | There is evidence that withdrawal reactions are less severe when the dose is tapered gradually over a period of several weeks according to the patient’s need. |
| 157 | There is no clear evidence that the SSRIs and related antidepressants have a significant dependence liability or show development of a dependence syndrome according to internationally accepted criteria … |
| 162 (2) | Upon review the EWG considered that the data to support the dose increases was inadequate. They considered that there was no evidence from clinical trials that increasing the dose above the recommended dose increases efficacy in the treatment of depression, SAD, GAD, PTSD and panic disorder. This review, combined with evidence from usage databases that a proportion of patients were being started on paroxetine at doses higher than those recommended, led CSM to advise that a reminder of the recommended dose of paroxetine should be sent to health professionals. |
| 163 (2) | These trials replicate the way that antidepressants are used in practice, and when the trial includes another group of patients who are taking placebo or another antidepressant, can provide evidence which tells us whether a treatment works. However, such trials do not provide evidence which tells us whether a dose increase was beneficial. |
| 165/6 | However, the data provide no evidence that there is an efficacy advantage from using doses above 20mg; in fact, the results on 20mg were numerically better than those for the higher doses. |
| 166 | There is also evidence of a dose response, with the trend favouring 60mg over 40mg. Hence there is some justification for concluding that some patients gain more benefit from 60mg than 40mg. |
| 166 | Panic disorder: Both the 10mg and 20mg doses failed to separate from placebo, but there is evidence of efficacy at 40mg, so the choice of 40mg as the recommended dose seems justified. |
| 166 | SAD, GAD and PTSD: The 20mg fixed dose achieved a clear statistically significant advantage over placebo, supporting the choice of 20mg as the recommended dose. There was no evidence of any additional benefit from using doses over 20mg; in fact, the results on 20mg were numerically better than those for the higher doses. |
| 167 (2) | There was evidence that 20-30mg had improved efficacy compared to lower doses, but no evidence that doses higher than this provided additional benefit. |
| 168 | There was evidence of a small efficacy advantage for 20mg over 10mg, but the number of withdrawals because of adverse events was also higher in the 20mg group. |
| 168 (4) | Depressive illness: Two fixed dose trials were conducted. The first of these was analysed as two trials; one in mild depression and one in moderate/severe depression. There was no evidence that fluoxetine was efficacious in mild depression, with none of the doses being superior to placebo. For moderate/severe depression, there was evidence that the 20mg dose was more efficacious than placebo, however the data provided no evidence that there is an efficacy advantage from using doses above 20mg, with the results on 20mg being numerically better than those for the higher doses. The second trial mainly contained moderate/severe patients. In this trial all three active doses produced similar efficacy, again providing no evidence that titrating above 20mg provides additional benefit, and suggesting that 5mg may be an efficacious dose, although it has been studied in too few patients to be confidently recommended. In both trials there were more withdrawals because of adverse events on higher doses, however this may be partly because patients were started on those doses and not titrated to them. |
| 169 | Bulimia nervosa: There was clear evidence that 60mg is superior to 20mg. The number of withdrawals because of adverse events was higher on the 60mg group, but this may be partly because patients were started on those doses and not titrated to them. |
| 170 | All (fluvoxamine) trials had a flexible dose design, so no evidence is available to support the recommendations to increase the dose. |
| 170 | However the (mirtazepine) trial clearly does not provide evidence to support a dose response relationship. |
| 172 | OCD: There was no evidence of increased efficacy (of sertraline) with increased dose in the single fixed dose trial. PTSD: All trials had a flexible dose design, so no evidence is available to support the recommendations to increase the dose. |
| 173 | Depressive illness: There were three fixed dose trials conducted (with venlafaxine). In the first trial the 225 and 375mg doses showed superiority over 75mg on the CGI-severity scale, and a trend for increasing efficacy with dose was shown on other endpoints. In the second trial a trend for increasing efficacy with dose was seen for HAM-D. The third trial did not provide evidence to support a dose response. An increased number of patients withdrew because of adverse events at doses above 200mg. |
| 173 | The groups were similar before titration while the venlafaxine group was superior after titration, providing some unorthodox but persuasive indirect evidence of a benefit of titrating those who do not respond to 75mg up to 150mg. |
| 173 | Venlafaxine - These trials established efficacy, but the benefit of dose increases cannot be established. There is no evidence to support starting on 150mg rather than 75mg in these patients. |
| 174 | There was no evidence of a dose response, however a dose response for venlafaxine ER in this indication might be inferred from the venlafaxine data (venlafaxine ER is merely an extended release formulation of venlafaxine). |
| 174 | Overall there was no evidence of a dose response above 75mg. In two trials the trend favoured 75mg over 150mg, while the ordering was reversed in the other two. (Venlafaxine in GAD) |
| 175 (5) | For the majority of SSRIs and related antidepressants there is no evidence that increasing the dose above the recommended dose provides additional benefit in depressive illness. There is no evidence for any the products of additional benefit from increasing the dose above that recommended in SAD, GAD or PTSD. This general lack of evidence of a dose response may, in part, reflect the difficulty of demonstrating efficacy in these indications against placebo in clinical trials, particularly in depressive illness. It may also reflect the inadequacy of the study designs. The trials conducted to look at dose response are not large enough, nor of a long enough duration, to identify whether there is a dose response relationship for serious adverse events. In the absence of good evidence it is a prudent assumption that some adverse events may increase with an increase in dose. In the absence of evidence of a benefit from increasing the dose, good practice would be to maintain patients on the lowest efficacious dose. |
| 175 | In the absence of evidence of a benefit from increasing the dose, good practice would be to maintain patients on the lowest efficacious dose. |
| 182 | There is epidemiological evidence that the risk of self-harm in depressed patients is greatest around the time of presentation to medical services. |
| 182 (3) | There is insufficient evidence from clinical trial data to conclude that there is any marked difference between members of the class of SSRIs, or between SSRIs and other antidepressants with respect to their influence on suicidal behaviour. Evidence from non-experimental studies based on the General Practice Research Database indicates that there is no increased risk of suicidal behaviour with SSRIs compared with TCAs. There is no clear evidence that there is an increased risk of self-harm or suicidal thoughts when SSRIs are discontinued. |
| 183 | Evidence of a relationship between suicidal behaviour and increasing/decreasing dose is not robust; however, patients should be monitored around the time of dose changes for any new symptoms or worsening of disease. |
| 183 | There is no clear evidence that the SSRIs and related antidepressants have a significant dependence liability or show development of a dependence syndrome according to internationally accepted criteria |
| 183 | In the absence of evidence of a benefit from increasing the dose, good practice would be to maintain patients on the lowest efficacious dose. |
| 184 | There is no clear evidence of an increased risk of self-harm and suicidal thoughts in young adults of 18 years or over. However, given that individuals mature at different rates and that young adults are at a higher background risk of suicidal behaviour than older adults, as a precautionary measure young adults treated with SSRIs should be closely monitored. |
| 184 | A systematic review of published and unpublished placebo-controlled RCTs of TCAs is required to assess whether there is any evidence of an increased risk of suicidal thoughts, self-harm and suicide in association with these drugs. |
| 184/5 | Likewise, there is emerging evidence that the risk of adverse drug reactions may be related to specific genotypes. |
| 186 | There is anecdotal evidence of an increased risk of self-harm early in antidepressant therapy; further investigation and quantification of this phenomenon will help inform the monitoring requirements for patients initiating antidepressant therapy. |
| 187 | These studies should be designed to provide clear evidence of any efficacy of increased doses. |
CLICK HERE TO RETURN TO THE MAIN ANALYSIS AND REVIEW OF
THE CSM EXPERT WORKING GROUP ON SSRI ANTIDEPRESSANTS