Tag: antidepressants

Categories : Mental HealthTags :

Are Psychedelics Better than Antidepressants? New Study Says No

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With an innovative approach, scientists try to get around the problem of participant expectation in tests of psychedelics.

Photo by Marek Piwnicki

Psychedelic-assisted therapy may be no more effective than traditional antidepressants when patients know what drugs they are actually taking, according to a first-of-its kind analysis that compared how well each type of drug worked for major depression.

Psychedelic-assisted therapy has resisted placebo-controlled testing methods, the gold standard in clinical trial design. Due to their powerful subjective effects, nearly everyone in the trial knows whether they received a psychedelic or the placebo even if they are not told.

But in trials of antidepressants, participants may not figure out whether they have received the drug or a placebo, which makes it hard to compare them with psychedelics.

To get around this problem, researchers from UC San Francisco, UCLA, and Imperial College, London tried a different approach. They compared the results from psychedelic therapy trials to the results from so-called open-label trials of traditional antidepressants, in which the participants all knew they were getting an antidepressant. That way, both treatments benefitted equally from the positive effect of patients knowing that they were being given a drug instead of a placebo. 

The findings both surprised and disappointed them: there was virtually no difference.

“Unblinding is the defining methodological problem of psychedelic trials. What I wanted to show is that even if you compare psychedelics to open-label antidepressants, psychedelics are still much better,” said Balázs Szigeti, PhD, a clinical data scientist at UCSF’s Translational Psychedelic Research Program, who led the study. “Unfortunately, what we got is the opposite result – that they are the same, which is very surprising given the enthusiasm around psychedelics and mental health.” 

Szigeti is the co-first author of the paper with Zachary J. Williams, MD, PhD, of UCLA; Hannah Barnett, MSc, of Imperial College, London is also an author. The study appeared March 18 in JAMA Psychiatry.

A sobering view

The hype around the use of psychedelics like psilocybin, or “magic mushrooms,” and LSD, to treat such conditions as depression and addiction has grown in recent years as an increasing number of studies have shown promising results, particularly for people who haven’t responded to traditional antidepressants.

The new findings don’t mean that psychedelic therapy does not work – just that it does not work better than traditional antidepressants. Patients improved substantially from both types of treatments, reducing depression scores by about 12 points on a standard scale.

Part of what has made psychedelics seem impressive in trials than antidepressants is how much more those who received the psilocybin or LSD improved than those who did not get it.

But the researchers concluded that this was the result of the lack of blinding in psychedelic trials: those who got the drug improved more because they knew they had gotten it, while those who received a placebo did worse because they knew they did not. Whereas in trials of traditional antidepressants, the difference between the groups was much smaller, making it seem like the drugs weren’t that effective.

When this ‘knowing the treatment’ factor leveled out, the seeming advantage of psychedelics disappeared. 

“Psychedelics may still be a valuable treatment option,” Szigeti said. “But if we want to understand their true benefits, we have to compare them fairly – and when we do that, the advantage over standard antidepressants is much smaller than many people, including myself, expected.”

Source: EurekAlert!

Categories : Substance Use UrogenitalTags :

Ketamine is Giving More Young People Bladder Problems – An Expert Explains

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A growing number of people in the UK are using ketamine recreationally. Photo by Colin Davis on Unsplash

Heba Ghazal, Kingston University

Urology departments in England and Wales have reported seeing an increase in the number of 16- to 24-year-olds being admitted for bladder inflammation associated with ketamine use.

This appears to coincide with an increase in ketamine use – with the number of adults and teens entering treatment for ketamine abuse last year jumping substantially compared to even just a few years previously.

Ketamine abuse can have many affects on the bladder, causing frequent urination, night-time urination, sudden urges, leakage, inflammation, pain in the bladder or lower back and blood in the urine. These symptoms can be severe, make daily life very difficult and may even be permanent in some cases.

Ketamine was first approved in 1970 for human use as an anaesthetic. More recently, studies have suggested that ketamine used at low doses may have antidepressant effects.

But a growing number of people are now using ketamine recreationally. It acts as a dissociative drug, causing users to feel detached from themselves and their surroundings. It can produce hallucinogenic, stimulant and pain-relieving effects, which last one to two hours.

Users typically snort or smoke powdered ketamine, or inject liquid ketamine or mix it into drinks in order to experience the drug’s effects. Snorting usually produces stronger effects and more noticeable symptoms than swallowing it.

Ketamine users can develop tolerance to the drug quickly, needing higher doses to get the same effects. This is probably due to the body and brain adapting to become more efficient at breaking down the drug. Frequent users often need to take twice the amount of occasional users to get the same effect.

Bladder damage

Frequent, high-dose ketamine use can cause serious damage to the bladder, urinary tract and kidneys. In severe cases, the bladder may need to be removed.

The first recorded cases of ketamine affecting the bladder were reported in Canada in 2007, where nine people who used ketamine recreationally had severe bladder problems and blood in their urine. Later, a bigger study in Hong Kong found the same issues in 59 people who had used ketamine for more than three months.

Ketamine, as with any other drug, is metabolised in the body where it’s broken down and excreted in urine.

When ketamine is broken down, it turns into chemicals that can seriously harm the bladder. When these by-products stay in contact with the urinary tract for a long time, they irritate and damage the tissue.

The bladder is damaged first, because it holds urine the longest. Later, the ureters (tubes connecting the kidney to the bladder) and the kidneys can also be affected.

Over time, the bladder can shrink and become stiff, causing strong urinary symptoms. The ureters can become narrow and bent, sometimes described as looking like a “walking stick.” This can lead to backed-up urine in the kidneys (hydronephrosis).

Ketamine also increases oxidative stress, which damages cells and causes bladder cells to die. This breaks the protective bladder lining, making it leaky and overly sensitive.

All these changes can make the bladder overactive, extremely sensitive and painful, often causing severe urges to urinate and incontinence.

Bladder damage from ketamine use happens in stages.

In the first stage, the bladder becomes inflamed. This can often be reversed by stopping ketamine and taking certain medication – such as anti-inflammatory drugs, pain relievers or prescription drugs that reduce bladder urgency and help the bladder lining heal.

In the second stage, the bladder can shrink or become stiff. In this stage, treatment is similar to stage one, but a bladder wash may also be required. This is where a catheter is used to put liquid medication directly into the bladder. The drug coats the bladder’s inner lining, helping to restore its protective layer and reduce inflammation.

Botulinum toxin injections may also be used to relax the bladder and reduce pain and urgency. Stopping ketamine remains essential to prevent further damage.

In the final stage, permanent damage occurs to the bladder and kidneys. Over time, if the kidneys are affected, it can lead to kidney failure. Dialysis (a treatment where waste products and excess fluid are filtered from the blood) or even surgery may be required to repair kidney function and the urinary system.

Although ketamine has been a class B drug since 2014, it’s unfortunately affordable and accessible – costing as little as £3 per gram in some parts of the UK. Raising awareness about the risks of ketamine use is essential to prevent these serious health problems.

Heba Ghazal, Senior Lecturer, Pharmacy, Kingston University

This article is republished from The Conversation under a Creative Commons license. Read the original article.

Categories : NeurologyTags :

Antidepressants not Linked to Serious Complications from TBI

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Taking certain antidepressants at the time of a traumatic brain injury (TBI) is not associated with an increased risk of death, brain surgery or longer hospital stays, according to a study published on January 28, 2026, in Neurology®, the medical journal of the American Academy of Neurology.

For the study, researchers looked at serotonergic antidepressants, which treat anxiety and depression by increasing serotonin activity in the brain. These included selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs) and tricyclic antidepressants (TCAs).

“Concerns have previously been raised that serotonergic antidepressants might increase the risk of bleeding in the brain or complicate early recovery after traumatic brain injury,” said study author Jussi P. Posti, MD, PhD, of the University of Turku in Finland. “However, our study found no evidence to support those concerns.” The study included 54 876 people in Finland who were 16 or older when hospitalised with a TBI. A total of 14% used serotonergic antidepressants at the time of the TBI.

Researchers reviewed national prescription records for preinjury antidepressant use and medical records to determine how many people died within a month, whether they needed emergency brain surgery, and how long they stayed in the hospital. A total of 4105 people died within a month. This included 7.6% of those taking antidepressants and 7.5% of people who did not. After adjusting for factors such as age, sex and other health conditions, researchers found people taking antidepressants before injury were no more likely to die within a month than those not taking them.

Antidepressant users were slightly less likely to require emergency brain surgery to relieve pressure or bleeding in the brain and prevent further damage. Of the total participants, 6.8% of the antidepressant users and 8.6% of those who did not use antidepressants needed emergency brain surgery. After adjustments, antidepressant users had an 11% lower risk. The amount of time in the hospital was the same for both groups.

“These findings provide reassurance for people who take antidepressants that antidepressant use does not appear to worsen early recovery after traumatic brain injury,” said Posti. “Future studies should examine whether these results hold true for long-term recovery and across different health care settings.”

A limitation of the study was that it was conducted only at hospitals and health care centres in Finland, so results may vary in other areas. The study was supported by the Finnish government, the Paulo Foundation, Paavo Nurmi Foundation, Research Council of Finland, Sigrid Jusélius Foundation and Finnish Foundation for Cardiovascular Research.

Source: American Academy of Neurology

Categories : Mental Health Neurodegenerative DiseasesTags :

Parkinson’s Drug Effective in Treating Persistent Depression

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In the largest clinical trial to date, pramipexole was found to be substantially more effective than a placebo at reducing the symptoms of treatment resistant depression (TRD) over the course of nearly a year, when added to ongoing antidepressant medication.

The trial, supported by National Institute for Health and Care Research (NIHR) and published in The Lancet Psychiatry, included 150 patients with treatment resistant depression, with equal numbers receiving 48 weeks of pramipexole or a placebo, alongside ongoing antidepressant medication.

Overall, the group taking pramipexole experienced a significant and substantial reduction in symptoms by week twelve of treatment, with the benefits persisting over the course of a year. However, there were also significant side effects, such as nausea, sleep disturbance and dizziness, with around one in five people on pramipexole dropping out of the trial as a result.

Professor Michael Browning, from the Department of Psychiatry, University of Oxford, and workstream lead in Mood Disorders for the NIHR Mental Health-Translational Research Collaboration (MH-TRC) Mission, who led the trial, said: ‘Effectively treating people who have not responded to first-line interventions for depression is a pressing clinical problem and there has long been an urgent need to find new treatments.

‘These findings on pramipexole are a significant breakthrough for patients for whom antidepressants and other treatments and therapies have not worked.

‘Pramipexole is a medicine licensed for Parkinson’s disease and works by boosting the brain chemical dopamine. This differs from the majority of other antidepressant medications which act on brain serotonin and may explain why pramipexole was so helpful in this study.

‘We now need more research focusing on reducing the side effects of pramipexole, evaluating its cost-effectiveness, and comparing it with other add-on treatments.’

Previous research into using the drug for depression had shown promise, but there had been limited data on its long-term outcomes and side effects until now.

Current guidelines for people with treatment resistant depression recommend adding new treatments, such as lithium or antipsychotics, to ongoing antidepressant treatment, but these have limited effectiveness and do not work for everyone.

Phil Harvey, 72, from Oxfordshire, was diagnosed with depression 20 years ago and tried different tablets and counselling but nothing worked. Eventually he had to take a year off work before retiring. He started on the trial in 2022.

He said: ‘Within a few weeks I felt the effects, it was amazing. I kept a diary which they gave us on how my mood was, motivation and how it improved. It was dragging me out of this dark black hole that I’ve been in for years.’

Participants were recruited from across the country, including as part of the NIHR-funded MH-TRC Mission mood disorder clinics, which are hosted at Oxford but located across the country. The clinics efficiently, and largely remotely, assess patients with difficult to treat mood disorders and offer them enrolment in research studies. The network can also support primary care services by providing assessment and treatment advice for patients who have not responded to initial treatment.

Source: University of Oxford

Categories : Mental HealthTags :

Large-scale Review Finds that Antidepressant Withdrawal Symptoms Are Rare

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The largest review of ‘gold standard’ antidepressant withdrawal studies to date has identified the type and incidence of symptoms experienced.

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The largest review of ‘gold standard’ antidepressant withdrawal studies to date has identified the type and incidence of symptoms experienced by people discontinuing antidepressants, finding most people do not experience severe withdrawal.

In a systematic review and meta-analysis of previous randomised controlled trials relating to antidepressant withdrawal, a team of researchers led by Imperial College London and King’s College London concluded that, while participants who stopped antidepressants did experience an average of one more symptom than those who continued or were taking placebos, this was not enough to be judged as significant. The results are out now in JAMA Psychiatry.

The most common symptoms were dizziness, nausea, vertigo and nervousness. Importantly, depression was not a symptom of withdrawal from antidepressants, and was more likely to reflect illness recurrence.

Researchers at Imperial College London, King’s College London, UCL and UK collaborators say their study provides much needed, clearer guidance for clinicians, patients and policymakers.

Dr Sameer Jauhar, lead author, at Imperial College London, said: “Our work should reassure the public because we replicated other findings, from high-quality studies, and have highlighted the clinical symptoms to look out for. Despite previous concern about stopping antidepressants, our work finds that most people do not experience severe withdrawal, in terms of additional symptoms. Importantly, depression relapse was not linked to antidepressant withdrawal in these studies, suggesting that if this does occur, people will need to see their health professional to rule out a recurrence of their depressive illness.”

Clinical academics from around the UK worked collaboratively to conduct the largest and most rigorous analysis of randomised controlled trials in antidepressant withdrawal, examining data from 50 trials across multiple conditions. The data involved a total of 17,828 participants, with an average age of 44 years, of whom 70% were female.  Two meta-analyses were conducted, one of the trials that used a standardised measure known as the Discontinuation Emergent Signs and Symptoms scale (DESS), and the other of the trials that used various other scales.

Across antidepressants, irrespective of type taken, the number of extra symptoms generally equated to one more symptom on the 43-symptom item scale. In placebo-controlled randomised controlled trials, the most common symptoms across antidepressants were dizziness (7.5% vs 1.8%), nausea (4.1% vs 1.5%), vertigo (2.7% vs 0.4%) and nervousness (3% vs 0.8%).

Experiencing just one symptom is below the 4 or more cutoff for clinically important discontinuation syndrome. 

The nature and rates of different symptoms varied between antidepressants, and some symptoms were also seen with placebo. This helped to clarify which symptoms were likely to be illness recurring, such as the participant relapsing into depression.

The data involved different types of antidepressants, including the serotonin-norepinephrine reuptake inhibitors (SNRIs) venlafaxine and duloxetine; the selective serotonin reuptake inhibitors escitalopram, sertraline and paroxetine; agomelatine, which is a melatonin receptor agonist and selective serotonin receptor antagonist; and vortioxetine, which inhibits the reuptake of serotonin as well as partial agonist and antagonist effects on various serotonin receptors.

The most symptoms were seen with discontinuance of venlafaxine, where approximately 20% of people suffered from dizziness, compared to 1.8% taking placebo. With vortioxetine, fewer than one extra symptom was seen on the standardised discontinuation scale. No extra symptoms were seen with agomelatine.

Adding non-placebo controlled studies increased these rates slightly; dizziness (11.8%, nightmares 8.1%, nervousness 7.6%, nausea 5.8%).

Relapse of depression was not seen in those withdrawing from antidepressants, even in people with existing depression.

The review included studies with different discontinuation regimes, but in the majority of studies (44), people either discontinued abruptly or tapered over 1 week.

Michail Kalfas, of the Institute of Psychiatry, Psychology & Neuroscience at King’s College London, said: “While uncommon, our study highlights that there could be a sub-group of people who develop more severe withdrawal symptoms than the wider population of antidepressant users. Our focus must now turn to look at the pharmacological basis for this reaction, and ask whether it relates to the way they metabolise these drugs.”

In terms of study limitations, 38 of the trials followed people up for up to two weeks post-discontinuation (the time period one would expect most discontinuation symptoms to occur), so researchers say this limits long-term conclusions. However, they note that findings from the 2021 UCL-led ANTLER trial involving long-term antidepressant users – which was included in this review – suggested severe withdrawal is infrequent, even after prolonged use.

The study follows recent concerns about the effects of stopping antidepressants, as well as various guidance changes on their prescribing. This current meta-analysis helps resolve the debate by showing that withdrawal is a real and drug-specific phenomenon, though not an inevitable outcome.

Source: Imperial College London

Categories : Cardiovascular Disease Mental HealthTags :

Extensive Study Refutes the Notion that Statins Have Antidepressant Effect

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Lipid-lowering medicines, known as statins, are prescribed in cases of high cholesterol levels, to reduce the risk of atherosclerosis, heart attack and stroke. The results of some small studies suggest that statins could also have an antidepressive effect. Researchers from Charité – Universitätsmedizin Berlin have now conducted an extensive study to investigate this claim. However, they could not verify that statins cause any additional antidepressive effects. As a result, the researchers suggest following the general guidelines and prescribing statins to help lower cholesterol, but not to manage depression. The study has now been published in JAMA Psychiatry.

Cholesterol-lowering drugs are the most commonly prescribed medicines globally. They have anti-inflammatory effects and lower the production of cholesterol in the liver, which in turn reduces the risk of developing cardiovascular diseases. In the past, numerous small studies have suggested that statins may also have antidepressive effects, alongside these more common properties. “If statins really did have this antidepressive effect, we could kill two birds with one stone,” says study leader Prof Christian Otte, Director of the Department of Psychiatry and Neurosciences on the Charité Campus Benjamin Franklin. “Depression and adiposity, or obesity, are among the most common medical conditions globally. And they actually often appear together: Those who are obese are at a higher risk of depression. In turn, those with depression are at a higher risk of obesity.” Obese patients often have higher cholesterol levels, so statins are administered to reduce the risk of cardiovascular diseases. But could they also alleviate depression?

An extensive, controlled study

Led by Christian Otte, the research team conducted a comprehensive study to investigate the potential antidepressive effects of statins that have been suggested. A total of 161 patients took part in the study, all of whom suffered from both depression and obesity. During the 12-week study, all participants were treated with a standard antidepressant (Escitalopram). Half of the participants also received a cholesterol-lowering drug (Simvastatin), while the other half were given a placebo. It was decided at random who would receive statins and who would be given the placebo – the recipients of each were unknown to both the medical team and the participants. This ensured a randomized and double-blind study that would produce reliable results. “This method should show us whether we can observe a stronger antidepressive effect among participants treated with statins, compared to those in the placebo group,” explains co-lead author Dr. Woo Ri Chae, Charité BIH Clinician Scientist at the Department of Psychiatry and Neurosciences.

The researchers used established clinical interviews and self-completed questionnaires to record the severity of depression in the patients at the beginning and end of the study. Blood samples were taken from the participants to determine their blood lipid levels and level of the C-reactive protein (CRP), which are known indicators of inflammatory processes in the body. “People with obesity and/or depression commonly exhibit slightly raised inflammatory markers in the blood. For some of those affected, this can actually be the cause of depression,” explains Christian Otte. “And this is precisely where we began with our hypothesis on the potential antidepressive effect of statins: If administering statins leads to an improvement in inflammatory markers, could this also possibly be accompanied by an antidepressive effect for some of the study participants?”

Traditional antidepressants remain the gold standard

At the beginning of the study, the participants ranged from moderately to severely depressed. Over the course of the 12-week study, the depression symptoms in all patients showed clear improvement – there was, however, no difference between those who received statins and those in the placebo group. “Administering the cholesterol-lowering drug improved blood lipid levels, as expected, and the inflammatory marker CRP also displayed a marked reduction,” says Woo Ri Chae. “So, unfortunately, this does not point to an additional antidepressive effect.” Christian Otte adds: “When it comes to treating depression, statins therefore have no additional benefit. To our present knowledge, traditional antidepressants remain the gold standard.” According to current guidelines, statins should be prescribed to reduce the risk of atherosclerosis and cardiovascular diseases. The researchers recommend that the same should naturally also apply for patients suffering from depression.

In further studies, Christian Otte’s team will conduct a more thorough analysis of the blood samples taken as part of this research on a cellular and molecular level, to reveal potential differences and correlations. The researchers are also continuing to work at full speed on improved strategies for treating patients with depression who also suffer from other conditions.

Categories : Mental HealthTags :

Three Quarters of People Who Have Taken Antidepressants Say They Were Helpful

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About 75% of a sample of nearly 20 000 people who have taken selective serotonin reuptake inhibitors (SSRIs) report they found them helpful, according to new research from the Institute of Psychiatry, Psychology & Neuroscience (IoPPN) at King’s College London.

Published in Psychological Medicine, the study explored different factors that could explain why SSRIs work for some people with major depressive disorder, but not others.

Researchers analysed data from UK Biobank on 19 516 participants who had tried at least one SSRI, such as citalopram, fluoxetine, paroxetine or sertraline, for at least two weeks. Participants reported whether the SSRI helped them “feel better” using a single item questionnaire with possible responses “yes, at least a little”, “no”, “do not know”, or “prefer not to answer”. This is the first detailed analysis of this large-scale study which assesses SSRIs using self-reported experiences rather than clinician-reported remission from symptoms.

Overall, 74.9% felt SSRIs helped them feel better. 18.8% said the prescribed drug was not helpful.

Using a range of data collected by UK Biobank, the study analysed what factors might influence whether people found SSRIs helpful.

It found that sociodemographic factors such as age, gender and household income were linked to differences in how people perceived the effectiveness of SSRIs. Those participants who were older, male, had lower incomes, and reported alcohol or illicit drug use were more likely to say that they did not find antidepressants helpful.

Participants who had experienced no mood improvement even when positive events occurred or whose worst episode of depression lasted more than two years, were also less likely to report that SSRIs were helpful. Lastly those who had a greater genetic risk for depression, calculated using polygenic risk scores, were less likely to report that SSRIs were helpful.

The use of antidepressants, and the rate at which they are prescribed in the UK, has been the source of much debate both in the public and media. While antidepressants don’t work for every user, this research provides reassuring evidence that many people report that this common type of medication is helping them manage what can be a severe illness.

Dr Michelle Kamp, Postdoctoral Research Associate at King’s IoPPN and first author on the study

We know that not all people respond to antidepressants prescribed, but most studies have focussed on clinician’s perspectives of response. Using participant reports, we found a strong support for antidepressants, with three quarters of people saying the drugs had helped them. The factors that make people more likely to respond to antidepressants mirror findings in clinical trials which use measures reported by clinicians. This suggests that patient-focussed responses can capture valuable insights into the effectiveness of antidepressants.

Professor Cathryn Lewis, Professor of Genetic Epidemiology & Statistics at King’s IoPPN and senior author on the study

Professor Andrew McIntosh, Professor of Biological Psychiatry at the University of Edinburgh’s Centre for Clinical Brain Sciences and co-investigator on the study, said: “The findings from this large study show that nearly three-quarters of people in UK Biobank who were treated with antidepressants found them helpful. There is already excellent evidence from clinical trials that antidepressants work for people with depression. However those studies focus on addressing only whether they are more effective than placebos, and not why they are more effective in some people than others. We must now focus on developing a better understanding of how antidepressants work and how we can predict which people are most likely to benefit from these treatments.”

The study offers key insights into antidepressant response, however the sample may not fully represent the general population and reliance on retrospective self-reports can lead to inaccurate recollection.

Source: King’s College London

Categories : Mental HealthTags :

Nearly Half of Depression Diagnoses Could be Considered Treatment-resistant

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Almost half of patients diagnosed with depression classify as being ‘treatment-resistant’ as new research suggests that many don’t respond to multiple antidepressant options.

The new study, published in the British Journal of Psychiatry was led by academics from the University of Birmingham and Birmingham and Solihull Mental Health NHS Foundation Trust. The study found that 48% of patients whose electronic healthcare records reported a diagnosis of depression had tried at least two antidepressants, and 37% had tried four or more different options.

Treatment-resistant depression (TRD) is typically defined as a form of depression that isn’t effectively managed after a patient tries two different antidepressants. There are currently few guidelines for treating TRD.

Patients who experience TRD were also invited to take part in interviews to share their experiences. Patients talked about a “sense of hopelessness” after trying multiple treatment options for the condition, and many shared their frustrations with a “one size fits all” approach to what works with treatment.

PhD researcher Kiranpreet Gill from the School of Psychology at the University of Birmingham and corresponding author of the study said:

“This paper highlights how widespread treatment-resistant depression is among those who are diagnosed with depression. With nearly half of all patients not responding to multiple drug options, we need better treatment options to be able to support patients for whom first line antidepressant medications don’t make a difference.

“Furthermore, the experiences of patients who took part in this study shows that more awareness and options for treating depression when first line antidepressant medications don’t work well is urgently needed.

“There is an irony that the experience of struggling to treat depression is in itself a risk factor for a worsening sense of ‘hopelessness’ as one patient described it. This should be a clarion call to recognise that treatment-resistant depression needs to be factored into clinical decision making and the ongoing support that patients are offered.”

There are increased risks of other psychiatric disorders among those with TRD such as anxiety, self-harm, and personality disorders, and physical health issues such as heart disease. Data analysis suggests that patients with TRD have 35% higher odds of having a personality disorder and 46% higher odds of cardiovascular disease and the combination with qualitative data suggests that patients have multiple and considerable barriers to achieving good health.

Professor Steven Marwaha, Clinical Professorial Fellow at the Institute for Mental Health at the University of Birmingham, a Consultant Psychiatrist at Birmingham and Solihull Mental Health NHS Foundation Trust, and co-author of the study said:

“This study is important as the data demonstrates people with TRD are at a higher risk of a range of poorer outcomes, and that we need better defined care pathways for helping this population, and are in urgent need of developing and testing new treatments for this group.”

Source: University of Birmingham

Categories : Mental HealthTags :

1 in 7 Patients Experience Symptoms After Discontinuing Antidepressants

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Approximately one in seven patients who discontinued their use of antidepressants experienced discontinuation symptoms, according to a wide-ranging analysis published in The Lancet Psychiatry. In arriving at this figure, the researchers accounted for a high frequency of anticipated discontinuation symptoms.

The emergence of adverse symptoms after antidepressant cessation has been described as far back as 1959, but was mostly neglected until the late 1990s. Today, the existence of antidepressant discontinuation symptoms is widely accepted, with transnational guidelines suggesting safe tapering. They can be highly variable and non-specific, with the most frequently reported symptoms being dizziness, headache, nausea, insomnia, and irritability. It has been reported that symptoms typically occur within a few days and are usually transient, but can last up to several weeks or months.

The incidence and severity of symptoms remained controversial however, with estimates ranging up to a majority (56%) of patients experiencing them, half of them severe. Previous reviews have been criticised for bias, and medical opinions are polarised on the subject.

The researchers reviewed 79 studies involving more than 21 000 participants, and found that about one-third of patients experienced symptoms such as headaches, nausea, insomnia, and irritability after accounting for patient expectations. Even in patients taking placebo, 17% experienced symptoms – suggesting that this is attributable to patient expectations about the adverse effects of stopping the drug.

After taking this into account, roughly one in seven individuals had antidepressant discontinuation symptoms. Neither tapering nor abrupt cessation of the drugs made no difference in the proportion of people who experienced discontinuation symptoms.

In addition, about 1 in 35 people experienced severe discontinuation symptoms. Desvenlafaxine, venlafaxine, imipramine, and escitalopram were associated with higher frequencies of discontinuation symptoms, and imipramine, paroxetine, and either desvenlafaxine or venlafaxine were associated with higher symptom severity. The authors cautioned that there was substantial heterogeneity of results.

Categories : Mental Health NeurologyTags :

Researchers Offer New Understanding of Antidepressant Mechanism

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Evidence suggests serotonin-boosting actions relieve depression by restoring normal communication and connections in the brain

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Researchers at the University of Colorado Anschutz Medical Campus have established a new framework for understanding how classic antidepressants work in treating major depressive disorder (MDD), reemphasising their importance and aiming to reframe clinical conversation around their role in treatment.

The nature of the dysfunction at the root of MDD has been under investigation for decades. Classic antidepressants, such as SSRIs (selective serotonin reuptake inhibitors, such as fluoxetine) cause an elevation in serotonin levels, a key neurotransmitter. This observation led to the idea that antidepressants work because they restore a chemical imbalance, such as a lack of serotonin.

But subsequent years of research showed no significant decrease in serotonin in people with depression. While experts have moved away from this hypothesis due to lack of concrete evidence, this has led to a shift in public opinion on the effectiveness of these medications.

Antidepressants, such as SSRIs and serotonin and norepinephrine reuptake inhibitors (SNRIs), are still effective in alleviating depressive episodes in many patients, however. In a paper published in Molecular Psychiatry, researchers outline a new framework for understanding how antidepressants are efficacious in treating MDD. This framework helps clarify how antidepressants like SSRIs can still be helpful, even if MDD isn’t caused by a lack of serotonin.

Evidence points to a communication problem

“The best evidence of changes in the brain in people suffering from MDD is that some brain regions are not communicating with each other normally,” said Scott Thompson, PhD, professor in the Department of Psychiatry and senior author. “When the parts of the brain responsible for reward, happiness, mood, self-esteem, even problem-solving in some cases, are not communicating with each other properly, then they can’t do their jobs properly,” Thompson said.

“There is good evidence that antidepressants that increase serotonin, like SSRIs, all work by restoring the strength of the connections between these regions of the brain. So do novel therapeutics such as esketamine and psychedelics. This form of neuroplasticity helps release brain circuits from being ‘stuck’ in a pathological state, ultimately leading to a restoration of healthy brain function,” Thompson said.  

Thompson and colleagues liken this theory to a car running off the road and getting stuck in a ditch, requiring the help of a tow truck to pull the car out of its stuck state, allowing it to move freely down the road again. Researchers are hoping healthcare providers will use their examples to bolster conversations with apprehensive patients about these treatments, helping them better understand their condition and how to treat it.

Study aims to reshape the conversation

“We are hoping this framework provides clinicians new ways to communicate the way these treatments work in combating MDD,” said C. Neill Epperson, MD, co-author of the paper and professor of the Department of Psychiatry at the CU School of Medicine.

“Much of the public conversation around the effectiveness of antidepressants, and the role serotonin plays in diagnosis and treatment, has been negative and largely dangerous,” Epperson said. “While MDD is a heterogenous disorder with no one-fits-all solution, it is important to emphasise that if treatments or medications are working for you, then they are lifesaving. Understanding how these medications promote neuroplasticity can help strengthen that message.”

Source: CU Anschutz Medical Campus