It's a phenomenon that holistic healing blogger Esther Louise knows all too well, having used antidepressants to successfully manage her lifelong battle with depression and anxiety. The benefits haven't come without some pitfalls, however. When starting the medication I tend to experience an increase in the severity of my symptoms for a short time before they slowly start to get better," she recalls.
She says that she still finds this experience to be very alarming, even though she's aware of what's going on. However, I try to remind myself that it is only temporary and these feelings will go away soon — in my case, they always have. This reaction probably occurs because it takes time for antidepressants to really kick in.
But therapeutic benefits are not expected for at least two weeks," Dr. Godot explains. Because something else has to happen in the brain and body, in response to the elevated neurotransmitter levels. And frankly, no one in the world knows exactly what that something is. Despite the risk of suicidal thoughts, antidepressant use seems to be a case of the good outweighing the bad, as research has shown that antidepressants typically have a protective effect against suicide.
A journal article also pointed put that toxicological reports of depressed people who died by suicide showed that it's more common for suicide to occur in patients who were not taking an antidepressant, than in those who were. It also appears that the risk of suicidal thoughts is far greater in children and adolescents taking these medications than those over the age of A review of 23 clinical trials using SSRIs in children and adolescents with depression found that there was a 4 percent risk for suicidal thoughts when using SSRIs versus a 2 percent risk when on a placebo.
This is with reference to the plausible demonstrative acts carried out by patient n. However, none of the two patients underwent affective temperament nor sub-threshold bipolarity assessment 27 , Specifically, patient n.
Yet, there is no FDA recommendation about the need to systematically assess sub-threshold bipolarity to date. Although suggestive and relevant from a clinical 6 and a methodological standpoint 35 , the actual potential impact of sub-threshold bipolarity in connection with suicidal ideation due to antidepressant exposure in some MDD cases is beyond the possibility of the present concise report.
Indeed, neither of the two patients exhibited overt manic switch or any over mixed features within the follow-up period. Nonetheless, both cases paradoxically document how neglected sub-threshold bipolarity assessment is in the clinical practice, including primary care It is also worth noticing that pivotal pharmaco-epidemiologic studies found a relationship between a higher number of sales or prescriptions of antidepressants and a lower suicide rate 37 — In particular, patient n.
Among other implications, the black box warning issued by the FDA could not determine any conclusive causal relationship. Depression represents a trans-diagnostic condition, and this is also why the antidepressant drug nomenclature seems outdated and misleading because of its disease-targeted approach in contrast to the novel neuroscience-based nomenclature, which seems more sound Milane et al.
Re-analysis of published data by Gibbons et al. Once again, this may suggest a possible differential developmental neurobiological profile among the cases that will be harmed by antidepressants, especially during adolescence or young adulthood vs.
Coupland et al. Above all, based on the present case reports, we suggest that the black box should finally be lifted, at least for adult patients, at least until further light can be shed over such an inconclusive and vividly debated matter. In other words, while the potential risk of induced suicide caused by antidepressants in children or adolescents or adults serves as a prompt for careful vigilance, the risk for over-concern among clinicians and patients, and the subsequent actual risk for suicidality due to the progression of the natural course of MDD, should likewise be appropriately counterbalanced.
The risk of suicide associated with untreated depression or anxiety disorder is high and represents a significant public health concern As pointed out by Friedman 52 , the FDA was aware of the need to balance the quantitatively small risk associated with antidepressant treatment against related proven benefits, yet it expanded the black-box warning issued in stating that depression itself is associated with an increased risk of suicide Roughly ten years have passed since the extended warning by the FDA and the subsequent alarm from some prescribing clinicians over-concerned about regulatory, license or insurance issues, as well as by patients or relatives exposed to stigmatization or incorrect information Also, the FDA may have accumulated additional data over the past decade, yet not allowed it to be released to the general public, potentially affecting the judgment of risk.
Interestingly, in the year , the FDA made an alert about antiepileptic drugs AEDs , stating that they may increase the risk of suicide. In that occasion, the scientific advisory committee voted against placing a black box warning on AEDs and suicide, although there was a significant positive association between AEDs and suicidality. The FDA attitude towards the AEDs may be perceived as a change in the position of the FDA over time, soliciting revision and updating of the black box label warning for antidepressant drugs.
The FDA expanded the black box warning already in the year , stating that depression carries an increased risk of suicide itself. Further revision is warranted 54 , placing further emphasis on the physician-patient interaction and the involvement of the caregivers, especially during the initial phase of the antidepressant treatment to reduce the risk for emergent suicidal ideation and self-harm. DD recorded the clinical information relevant to the present report.
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. World Health Organization Google Scholar.
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Ann Gen Psychiatry J Affect Disord — Prevalence and clinical features associated with bipolar disorder polypharmacy: a systematic review. Neuropsychiatr Dis Treat Patient adherence in the treatment of depression. Br J Psychiatry —9. Mungo S, Fornaro M. Adherence to chronic therapies in psychiatry: from treatment to cure. J Psychol Psychother S Researchers there found a positive association between suicide rates and antidepressant prescriptions. What it indicates is that in Japan, both suicide rates and use of antidepressants increase with age; however, for a given age-group, suicide rates have decreased with increasing SSRI prescriptions over time.
Another anomaly is Iceland, where antidepressant prescription rates seemed unrelated to lower suicide rates. Part of the reason for this are the traditionally extremely low suicide rates in Iceland. This is a floor effect; there is so little room for a further decline in suicide rates that the relationship to prescription rates is extremely hard to detect. Italy has had a decline in suicide rates linked to prescriptions for women but not for men.
Most antidepressants in Italy are prescribed for women, and so the ability to detect such a relationship is greater in women. Ecological modeling from large numbers of small areas can also provide a stronger basis for understanding the association between antidepressant medication use and suicide completion.
US county-level data on suicide rates and antidepressant prescription rates were analyzed for to This finding has been replicated in children and young adolescents aged 5 to 14 years and indicates that the relationship is robust and manifest across the life cycle, from childhood to adulthood.
Large-scale observational studies. Valuck and colleagues 11 examined the effects of antidepressants on 24, adolescents with a first diagnosis of major depression.
At least 6 months of follow-up data were available, which showed that treatment with SSRIs, other antidepressants, or combinations of antidepressants did not increase the risk of suicide attempts. Similar results were seen by Simon and colleagues. Tiihonen and colleagues 15 found that current antidepressant use was associated with increased risk of suicide attempts but lower risk of suicide completion in youths who had been treated with an antidepressant.
Analyses stratified by age showed that the benefit for to year-olds was comparable to that for the older age-groups: this contrasts with the FDA findings of greater risk in young adults that prompted the extension of the black box warning to include this age-group. The lack of detectable benefit 9 months later may reflect a combination of spontaneous remission of major depression in the placebo group and declining compliance over time with treatment in the medicated group.
Randomized controlled trials. In our research synthesis of longitudinal data, fluoxetine in youths, adults, and the elderly and venlafaxine in adults were shown to be efficacious in all age-groups. Children experienced the maximum benefit and the elderly only marginal benefit following 6 weeks of treatment. Figure 4 reveals that over time in both treated and control patients, there was a decrease in the frequency of suicidal thoughts and behavior; however, the decrease was significantly more pronounced in patients randomized to antidepressant treatment.
The magnitude of the difference between active treatment and control in terms of suicidal thoughts and behavior increases over time in adults and the elderly; however, there was no effect of treatment on suicidal thoughts and behavior in children, despite statistically and clinically significant benefits in terms of depression observed with active treatment. These findings suggest that suicidal thoughts and behavior in adults are largely driven by depression severity; however, this does not appear to be the case for children.
Clinicians who treat adults need to focus on maximizing the degree of improvement in depression to maximize the decrease in suicidal ideation and thereby acute suicide risk. Ecological studies revealed that there may have been unintended consequences of the black box warning.
Evidence now shows that antidepressant prescription rates dropped precipitously beginning with the public health advisory in March , which preceded the black box warning in October Isacsson and Ahlner26 looked at suicides in the to year-old group in Sweden from through After the warning, the suicide rate increased for 5 consecutive years Busch and colleagues 27 studied academic and behavioral outcomes in more than , adolescents aged 12 to 17 using a difference-in-difference design.
They found that grade point averages GPAs for depressed children decreased 0. They also found increases in delinquency and use of tobacco and illicit drugs among depressed adolescents. The FDA implementation of a black box warning had the purpose of reducing suicide rates in children, adolescents, and young adults. The picture following the FDA warning and implementation of the black box warning is not that of a lower suicide rate as intended or hoped for by the FDA.
Instead, we see fewer antidepressant prescriptions, an increase in youth suicides, and negative effects on human capital. That outcome is difficult to reconcile with a model of an increase in youth suicide risk when antidepressants are prescribed. The findings fit better with a model of a net reduction in suicide risk when antidepressants are prescribed. The data show that in adults, antidepressants appear to protect against suicidal events.
Antidepressants are effective in reducing symptoms, which, in turn, mediates suicidal events in adults and the elderly. This does not appear to be the case for youths, for whom antidepressant medications can reduce the severity of depression but appear to have no effect one way or the other on suicidal thoughts and behavior.
Conversely to what is seen in adults, it may be that aggressive-impulsive traits play a more important role in youth suicide than does depressed mood.
The impact of antidepressants on these traits remains unclear. Youth suicide may also be potentially related to illicit drug use and social factors, such as bullying, that are not directly affected by antidepressants. The black box warning and the earlier public health advisory have shown that discouraging the medication treatment of depression in children is not an effective solution in preventing suicidal behavior.
Careful monitoring and treatment of depression and monitoring suicide risk in children is clearly essential.
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