If you want to taper off the Lexapro and you are not sure where to start, you can click here and read the bestselling book, How to Get Off Psychoactive Drugs Safely or send Jim Harper an email at [email protected] and he will guide you through the process of Lexapro withdrawal.
If you are experiencing Lexapro withdrawal brain zaps, electrical jolts in the head, click here
Potential Lexapro side effects while taking Lexapro click here
The reason you started Lexapro may be similar to one of the stories below. The good news for these people, they used The Road Back Program and are now off Lexapro and Lexapro withdrawal is a distant memory.
“I have been on Lexapro for almost a month. The side effects are horrible. I can’t think clearly, I feel like I am unable to carry on conversations. I have no appetite. I feel my mind has slipped. This is a terrible drug.”
“I was given samples of 10mg Lexapro tabs to help with anxiety associated with menopause. After the first dose I felt like I had taken speed. My blood pressure was off the charts, my head ached, my heart was pounding and my mouth was dry down to my stomach. I couldn’t eat. It took over 24 hours for the effects to wear off. Never again.”
“I was prescribed Lexapro after my therapist claimed I have BPD. I only took the 10 MG tablet ONCE and these were what happened: I felt like I was tripping on acid, I could barely breathe, I went from depressed to extremely agitated in a
very short time, I went from really tired after taking it to extremely awake, I didn’t dream at all that night, I was still feeling funky the next day, and people claim it isn’t until weeks into treatment you finally see side affects-HAH! I will never take this drug again-and I switched therapists!”
“Lexapro caused me vivid dreams, profuse sweating, leg muscle cramps, severe wrist and hand pain, arthritic type pain in most all joints – hate it.”
“My doctor gave me a few weeks worth to try. I gained weight, then more weight, then more. I put on 14 pounds in two weeks!!! I also felt as though it did not relieve my feelings of anxiety.”
“I requested Lexapro to my doctor as a means of dealing with symptoms associated with a disk hernia, work related stress and anxiety I am experiencing in relation to these two issues. I have experienced increased fatigue, anxiety, head and neck pain, sinus pain, dry skin, itching, confusion, increased sweating (especially at night) with at the same time as having the chills, nausea and a feeling of the need to vomit, frequent urination, body aches, painful joints and popping/cracking joints as well as a whole host of less bothersome side affects. I’ve found that I have increased appetite, lethargy and constant, energy draining feverish symptom that never seems to go away. This winter I used the medication for a couple of months or so but did not seems to experience all the side affects that I have this summer. It seems to me that heat and/or sun causes more adverse reaction for me. I feel so worn down with this drug. It just seems to exacerbate my original problems!
I am more depressed, more anxious, more agitated and irritable and more uncomfortable than I was before beginning taking the product. I would be cautious using Lexapro and advise my physician immediately if or when you have any serious side effects that are particularly bothersome for you. I think I’m going to try something else or seeks some sort of alternative treatments. I am extremely uncomfortable taking it.”
“I was prescribed Lexapro for anxiety and mild depression. I didn’t notice any side effects at first. I was told by the pharmacist that there weren’t really any. I have been on Lexapro now for about 6 months. I have gained about 15-20 pounds in that time. That is why I came online looking to see if this was possibly due to the medicine. I only take 10 mg a day, but I am still eating about the same as I did before. Yes, it is very frustrating. After reading some of the postings on this website, I think I am having some other side effects that I didn’t even realize. I am tired a lot. I don’t have a lot of energy. I think it is time to see the doctor again.”
“4 weeks ago my doctor increased my dosage of Lexapro to 20 mg. from l5 mg. In the last week I have experienced fluctuation in blood pressure, my usual pressure is l00/60 and the pressure about an hour or less upon awakening in a.m. was reading 88/59, one day in the afternoon it was 77/49. My internal med doctor is suggesting I lower the meds to l5 mg. and see if these readings improve, I also have constipation, nausea, gastrointestinal discomfort, burping, etc. I am getting palpitations, headaches.”
There is Hope. There is a Solution
Lexapro belongs to a class of medications known as selective serotonin reuptake inhibitors (SSRIs) and partial agonists of the serotonin 1A receptor. The drug works by increasing the levels of serotonin in the brain, which is a neurotransmitter that is responsible for regulating mood, appetite, and sleep.
One of the primary advantages of Lexapro is its low incidence of side effects compared to other antidepressants. While most SSRIs are associated with side effects such as weight gain, sexual dysfunction, and drowsiness, Lexapro has been shown to cause significantly fewer side effects in clinical trials.
Some of the most common side effects of Lexapro include diarrhea, nausea, and vomiting. However, these side effects are typically mild and go away on their own after a few days. Less common side effects may include sleep disturbances, dizziness, and dry mouth.
Lexapro is available in tablet form and is typically taken once daily with food. The recommended starting dose is 10 milligrams (mg) per day, which can be increased to 20 mg per day after one week. Patients who do not respond to the 20 mg dose may be increased to 40 mg per day.
Full Description of Lexapro Escitalopram:
Lexapro is a medication that is used to treat major depressive disorder. It is an antidepressant medication that works by increasing the levels of serotonin in the brain. Like any medication, Lexapro can have side effects, and some people may experience withdrawal symptoms when they stop taking it.
Withdrawal symptoms can occur when a person stops taking Lexapro suddenly, or when they taper off the medication too quickly. Withdrawal symptoms can vary in severity and duration, depending on the individual and how long they have been taking the medication. Some common withdrawal symptoms of Lexapro include:
1. Dizziness: Some people may experience dizziness or lightheadedness when they stop taking Lexapro. This can make it difficult to perform daily activities such as driving or working.
2. Nausea: Nausea and vomiting are common withdrawal symptoms of Lexapro. These symptoms can be severe and may last for several days.
3. Insomnia: Some people may experience insomnia or difficulty sleeping when they stop taking Lexapro. This can make it difficult to get a good night’s sleep and can lead to fatigue and other health problems.
4. Anxiety: Lexapro is used to treat anxiety as well as depression, so it is not surprising that some people may experience anxiety when they stop taking the medication. This can include feelings of restlessness, nervousness, and panic.
5. Mood swings: Lexapro can help to stabilize mood, so when people stop taking it, they may experience mood swings or changes in their emotional state. This can include feelings of irritability, sadness, or agitation.
6. Headaches: Some people may experience headaches or migraines when they stop taking Lexapro. These can be mild to severe and can make it difficult to perform daily activities
7. Flu-like symptoms: Some people may experience flu-like symptoms when they stop taking Lexapro. These can include fever, chills, and body aches.
If you are experiencing withdrawal symptoms from Lexapro, it is important to talk to your doctor. Your doctor may recommend gradually tapering off the medication to reduce the severity of withdrawal symptoms. They may also prescribe other medications or therapies to help manage withdrawal symptoms.
Lexapro withdrawal
Lexapro Withdrawal
Lexapro Withdrawal
Lexapro Withdrawal
Get relief from Lexapro insomnia and Lexapro anxiety.
Lexapro withdrawal solution.
Lexapro Withdrawal
The F.D.A. estimates 10% of the people withdrawing off an antidepressant will not be able to succeed due to withdrawal side effects. Lexapro is not different. If you are one of the lucky 90% that can do a successful Lexapro withdrawal you still need to rebuild your body once off Lexapro. This site provides information what to do for Lexapro withdrawal and after Lexapro withdrawal if you were able to succeed on your own.
Let’s take at how to have a successful Lexapro withdrawal first. There are two parts that make a successful Lexapro withdrawal possible. How you reduce the Lexapro during withdrawal and taking a few supplements that will help eliminate any Lexapro withdrawal side effects. If you want to read the short version of how to handle Lexapro withdrawal side effects, Click here. Page opens new browser window.
It does not matter what dosage of Lexapro you are taking or how long you have used Lexapro; the reduction of Lexapro is the same. You want to reduce Lexapro by no more than 10% and only reduce by an additional 10% every 2 weeks. This is the safest and most successful way to become Lexapro free and not suffer during withdrawal.
Check with your pharmacist for compounding the Lexapro and the best option. The next best method is to use a pill slicer and a milligram scale. Get a 7 day pill holder and once a week cut your pills for the coming week. Roughly 90% of you will be able to complete a Lexapro withdrawal using the method above. However, you will most likely experience flu like symptoms, headache, brain zaps, anxiety, and insomnia or in some cases extreme fatigue. These symptoms will normally last 1 or 2 weeks.
In early 1999, we began investigating the use of natural supplements to help ease withdrawal symptoms. Over the past 20 plus years we have continued to improve this approach and our success rate is rather high. With Lexapro withdrawal, you should take 4 supplements. JNK Formula Complete, Neuro Day, Neuro Night and Omega 3 Supreme.
You can read The Program (link above) for all chapters of the bestselling book, How to Get Off Psychoactive Drugs Safely, or just follow the instructions on each bottle to know when to take each supplement. Take the supplements for 1 full week before reducing the Lexapro and then you can begin your Lexapro withdrawal reduction. It really can be this simple. If you are located in the United States Canada, Great Britain Click here
What is Lexapro
Lexapro is a prescription medication used to treat depression and anxiety. It belongs to a class of drugs known as selective serotonin reuptake inhibitors (SSRIs). The medication takes some time to build up in the body, which is why it can take a few weeks before people begin noticing a reduction in symptoms of depression or anxiety. If you suddenly stop taking Lexapro, however, you may experience symptoms of withdrawal. In the United States this withdrawal is known as Lexapro Discontinuation Syndrome but in Europe is known as Lexapro Withdrawal. Antidepressants are among the most commonly prescribed medications in the United States. Of the more than 60 million people who take them in a given month, about one quarter have been taking them for more than 10 years. Often, long- term use is linked to fear of relapse of their symptoms or withdrawal. We have found length of time taking Lexapro WILL NOT determine how easy or difficult it will be for you to accomplish a Lexapro withdrawal.
People experience symptoms of Lexapro withdrawal because of the way SSRI’s work in the brain. SSRIs affect the levels of serotonin, a type of mood-regulating neurotransmitter in the brain. When you abruptly stop taking your medication, it doesn’t give the brain enough time to adjust to the sudden change. Whether you are stopping Lexapro because it is not working for you or you are better and you’ve decided with your doctor that it makes sense to come off your medication, the quitting process needs to be slow and gradual.
Recent research has found that the severity of SSRI withdrawal is much worse than previously believed. On average, about 46% of people experiencing SSRI withdrawal symptoms describe them as severe. Severe symptoms indicate that withdrawal can potentially interfere with your ability to meet responsibilities at home and at work.
It was also found that 10% of the people attempting antidepressant withdrawal, 10% quit the Lexapro withdrawal due to a withdrawal side effect known as brain zaps. The Omega 3 Supreme used during Lexapro withdrawal is formulated to ease this severe withdrawal side effect.
Most Common Symptoms
The most common symptoms of Lexapro withdrawal—occurring in more than one in four people—are as follows:
Dizziness
Muscle tension
Chills
Confusion
Trouble concentrating
Trouble remembering things
Crying
The most common symptoms of Lexapro withdrawal are dizziness, muscle tension, and chills, which each affect about 44% of users. Many people also experience confusion and difficulty concentrating. Once again, the supplements have been formulated to help with these symptoms.
Complete Symptoms
The following is a more complete list of symptoms associated with withdrawal: Changes in motor control: Tremors, muscle tension, restless legs, unsteady gait, or difficulty controlling speech and chewing movements Digestive issues: Nausea, vomiting, cramps, diarrhea, or appetite loss Flu-like symptoms: Headache, muscle pain, weakness, and tiredness. Instability: Dizziness, lightheadedness, difficulty walking Mood changes: Anxiety, agitation, panic, suicidal ideation, depression, irritability, anger, mania, or mood swings Sleep problems: Nightmares, unusual dreams, excessive/vivid dreams, or insomnia
Unusual sensations: Brain zaps (like an electrical shock or shiver in your brain), pins and needles, ringing in the ears, strange tastes, or hypersensitivity to sound.
Lexapro withdrawal can take a real toll on your life, both physically and emotionally. Antidepressants like Lexapro work by increasing serotonin levels in your brain. When you stop taking them, it takes your brain a while to get used to the drug’s absence. Unfortunately, the amount of time this takes can vary widely.
Lexapro withdrawal symptoms typically arrive one to three days after your last dose. It can start sooner (within hours) or later (more than a week). This is why most inpatient facilities fail with Lexapro withdrawal. Insurance may pay only 9 days of treatment and by the time you are off the plane near your city, Lexapro withdrawal is back and in full effect. Lexapro withdrawal should never be rushed.
Coping & Relief
The best way to find relief from Lexapro withdrawal is to use the supplements mentioned above, reduce the Lexapro gradually and only continue to reduce when you are feeling very well. If you are still experiencing symptoms of depression, definitely send us an e-mail and we will help you adjust supplements and assist you in finding the cause.
Taper Off Medication Slowly
In 1999, our founder, Jim Harper, published a guideline for reducing medications. That guideline has been adapted to all psychoactive medications by the drug manufacturers. The most effective way to minimize symptoms of withdrawal is to slowly taper off your medication. “Reduce the medication slowly. If withdrawal symptoms begin go back up to the last dosage you were doing fine at, stay at that dosage until all withdrawal has subsided. When you continue with withdrawal reduce the medication slower than the previous reductions.
”Lexapro should only be reduced by 10%. Some people will need to reduce the Lexapro by 5%. Reductions of the Lexapro can be made every 7 days or in some cases every 14 days. Slow and steady wins this race.
Tapering involves adjusting your dose by a small amount, gradually decreasing until your body gets used to lower levels of the medication. Talk to your doctor who can then create a dose schedule and carefully monitor the process to avoid severe symptoms. Practice Good Self-Care Taking good care of your health as you stop taking Lexapro can also help you to better manage any withdrawal symptoms that you experience.
Some steps you can take that might help you cope with withdrawal symptoms include:
Do not change your diet when tapering. This can alter metabolism rate of the Lexapro and create a withdrawal symptom.
Follow your doctor’s tapering recommendations
Get plenty of rest
Get regular mild exercise
Get support from family, friends, or support groups
If you or someone you love shows any of the following signs or symptoms after stopping or during a Lexapro taper, get help:
Becoming preoccupied with death, dying, or violence Engaging in risky or self-destructive activities, such as driving drunk Feeling hopeless or trapped Gathering the means to commit suicide, such as bullets or pills Getting affairs in order or giving away belongings Having intense mood swings.
Planning how you would commit suicide if you were going to do it Saying goodbye to people as if it were the last time Talking or thinking about suicide more than normal, for example, “I wish I were dead”
1. Withdrawal Symptoms after Selective Serotonin Reuptake Inhibitor Discontinuation: A Systematic Review
Background: Selective serotonin reuptake inhibitors (SSRI) are widely used in medical practice. They have been associated with a broad range of symptoms, whose clinical meaning has not been fully appreciated. Methods: The PRISMA guidelines were followed to conduct a systematic review of the literature. Titles, abstracts, and topics were searched using the following terms: ‘withdrawal symptoms’ OR ‘withdrawal syndrome’ OR ‘discontinuation syndrome’ OR ‘discontinuation symptoms’, AND ‘SSRI’ OR ‘serotonin’ OR ‘antidepressant’ OR ‘paroxetine’ OR ‘fluoxetine’ OR ‘sertraline’ OR ‘fluvoxamine’ OR ‘citalopram’ OR ‘escitalopram’. The electronic research literature databases included CINAHL, the Cochrane Library, PubMed and Web-of-Science from inception of each database to July 2014. Results: There were 15 randomized controlled studies, 4 open trials, 4 retrospective investigations, and 38 case reports. The prevalence of the syndrome was variable, and its estimation was hindered by a lack of case identification in many studies. Symptoms typically occur within a few days from drug discontinuation and last a few weeks, also with gradual tapering. However, many variations are possible, including late onset and/or longer persistence of disturbances. Symptoms may be easily misidentified as signs of impending relapse. Conclusions: Clinicians need to add SSRI to the list of drugs potentially inducing withdrawal symptoms upon discontinuation, together with benzodiazepines, barbiturates, and other psychotropic drugs. The term ‘discontinuation syndrome’ that is currently used minimizes the potential vulnerabilities induced by SSRI and should be replaced by ‘withdrawal syndrome’.
2. Selective serotonin reuptake inhibitors for premenstrual syndrome
Background: Premenstrual syndrome (PMS) is a common cause of physical, psychological and social problems in women of reproductive age. The key characteristic of PMS is the timing of symptoms, which occur only during the two weeks leading up to menstruation (the luteal phase of the menstrual cycle). Selective serotonin reuptake inhibitors (SSRIs) are increasingly used as first line therapy for PMS. SSRIs can be taken either in the luteal phase or else continuously (every day). SSRIs are generally considered to be effective for reducing premenstrual symptoms but they can cause adverse effects.
Objectives: The objective of this review was to evaluate the effectiveness and safety of SSRIs for treating premenstrual syndrome.
Search methods: Electronic searches for relevant randomised controlled trials (RCTs) were undertaken in the Cochrane Menstrual Disorders and Subfertility Group Specialised Register, Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library), MEDLINE, EMBASE, PsycINFO, and CINAHL (February 2013). Where insufficient data were presented in a report, attempts were made to contact the original authors for further details.
Selection criteria: Studies were considered in which women with a prospective diagnosis of PMS, PMDD or late luteal phase dysphoric disorder (LPDD) were randomised to receive SSRIs or placebo for the treatment of premenstrual syndrome.
Data collection and analysis: Two review authors independently selected the studies, assessed eligible studies for risk of bias, and extracted data on premenstrual symptoms and adverse effects. Studies were pooled using random-effects models. Standardised mean differences (SMDs) with 95% confidence intervals (CIs) were calculated for premenstrual symptom scores, using separate analyses for different types of continuous data (that is end scores and change scores). Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated for dichotomous outcomes. Analyses were stratified by type of drug administration (luteal or continuous) and by drug dose (low, medium, or high). We calculated the number of women who would need to be taking a moderate dose of SSRI in order to cause one additional adverse event (number needed to harm: NNH). The overall quality of the evidence for the main findings was assessed using the GRADE working group methods.
Main results: Thirty-one RCTs were included in the review. They compared fluoxetine, paroxetine, sertraline, escitalopram and citalopram versus placebo. SSRIs reduced overall self-rated symptoms significantly more effectively than placebo. The effect size was moderate when studies reporting end scores were pooled (for moderate dose SSRIs: SMD -0.65, 95% CI -0.46 to -0.84, nine studies, 1276 women; moderate heterogeneity (I(2) = 58%), low quality evidence). The effect size was small when studies reporting change scores were pooled (for moderate dose SSRIs: SMD -0.36, 95% CI -0.20 to -0.51, four studies, 657 women; low heterogeneity (I(2)=29%), moderate quality evidence).SSRIs were effective for symptom relief whether taken only in the luteal phase or continuously, with no clear evidence of a difference in effectiveness between these modes of administration. However, few studies directly compared luteal and continuous regimens and more evidence is needed on this question.Withdrawals due to adverse effects were significantly more likely to occur in the SSRI group (moderate dose: OR 2.55, 95% CI 1.84 to 3.53, 15 studies, 2447 women; no heterogeneity (I(2) = 0%), moderate quality evidence). The most common side effects associated with a moderate dose of SSRIs were nausea (NNH = 7), asthenia or decreased energy (NNH = 9), somnolence (NNH = 13), fatigue (NNH = 14), decreased libido (NNH = 14) and sweating (NNH = 14). In secondary analyses, SSRIs were effective for treating specific types of symptoms (that is psychological, physical and functional symptoms, and irritability). Adverse effects were dose-related.The overall quality of the evidence was low to moderate, the main weakness in the included studies being poor reporting of methods. Heterogeneity was low or absent for most outcomes, though (as noted above) there was moderate heterogeneity for one of the primary analyses.
3. Kappa opioid receptor in nucleus accumbens regulates depressive-like behaviors following prolonged morphine withdrawal in mice
Prolonged withdrawal from opioids leads to negative emotions. Kappa opioid receptor (KOR) plays an important role in opioid addiction and affective disorders. However, the underlying mechanism of KOR in withdrawal-related depression is still lacking. We found that escitalopram treatment had a limited effect in improving depression symptoms in heroin-dependent patients. In mice, we demonstrated prolonged (4 weeks) but not acute (24 h) withdrawal from morphine induced depressive-like behaviors. The number of c-Fos positive cells and the expression of KOR in the nucleus accumbens (NAc), were significantly increased in the prolonged morphine withdrawal mice. Conditional KOR knockdown in NAc significantly improved depressive-like behaviors. Repeated but not acute treatment with the KOR antagonist norBNI improved depressive-like behaviors and reversed PSD95, synaptophysin, p-ERK, p-CREB, and BDNF in NAc. This study demonstrated the important role of striatal KOR in morphine withdrawal-related depressive-like behaviors and offered therapeutic potential for the treatment of withdrawal-related depression.
4. Are all antidepressants the same? The consumer has a point
Background: Although a large variety of antidepressants agents (AD) with different mechanisms of action are available, no significant differences in efficacy and safety have been shown. However, there have been few attempts to incorporate data on subjective experiences under different AD.
Method: We conducted a qualitative and quantitative analysis of the posts from the website www.askapatient.com from different AD. We reviewed a random sample of 1000 posts.
Result: After applying the inclusion and exclusion criteria, we included a final sample of 450 posts, 50 on each of the most used AD: sertraline, citalopram, paroxetine, escitalopram, fluoxetine, venlafaxine, duloxetine, mirtazapine, and bupropion. Bupropion, citalopram, and venlafaxine had the higher overall satisfaction ratings. Sertraline, paroxetine, and fluoxetine had high reports of emotional blunting, while bupropion very few. Overall satisfaction with AD treatment was inversely associated with the presence of the following side-effects: suicidality, irritability, emotional blunting, cognitive disturbances, and withdrawal symptoms. After adjusting for confounders, only emotional blunting was shown to be more frequently reported by users of serotonergic agents, as compared to non-serotoninergic agents.
Conclusion: This research points out that the subjective experience of patients under treatment should be taken into consideration when selecting an AD as differences between agents were evident. In contrast to the more frequent treatment decisions, users might prefer receiving a non-serotoninergic agent over a serotonergic one due to their lower propensity to produce emotional blunting.
5. Escitalopram Ameliorates Cognitive Impairment in D-Galactose-Injected Ovariectomized Rats: Modulation of JNK, GSK-3β, and ERK Signalling Pathways
Though selective serotonin reuptake inhibitors (SSRIs) have been found to increase cognitive performance in some studies on patients and animal models of Alzheimer’s disease (AD), other studies have reported contradictory results, and the mechanism of action has not been fully described. This study aimed to examine the effect of escitalopram, an SSRI, in an experimental model of AD and to determine the involved intracellular signalling pathways. Ovariectomized rats were administered D-galactose (150 mg/kg/day, i.p) over ten weeks to induce AD. Treatment with escitalopram (10 mg/kg/day, p.o) for four weeks, starting from the 7th week of D-galactose injection, enhanced memory performance and attenuated associated histopathological changes. Escitalopram reduced hippocampal amyloid β 42, β-secretase, and p-tau, while increasing α-secretase levels. Furthermore, it decreased tumor necrosis factor-α, nuclear factor-kappa B p65, and NADPH oxidase, while enhancing brain-derived neurotrophic factor, phospho-cAMP response element binding protein, and synaptophysin levels. Moreover, escitalopram diminished the protein expression of the phosphorylated forms of c-Jun N-terminal kinase (JNK)/c-Jun, while increasing those of phosphoinositide 3-kinase (PI3K), protein kinase B (Akt), glycogen synthase kinase-3β (GSK-3β), extracellular signal-regulated kinase (ERK) and its upstream kinases MEK and Raf-1. In conclusion, escitalopram ameliorated D-galactose/ovariectomy-induced AD-like features through modulation of PI3K/Akt/GSK-3β, Raf-1/MEK/ERK, and JNK/c-Jun pathways.
7. Calcium-dependent intracellular signal pathways in primary cultured adipocytes and ANK3 gene variation in patients with bipolar disorder and healthy controls
Bipolar disorder (BD) is a chronic psychiatric disorder of public health importance affecting >1% of the Swedish population. Despite progress, patients still suffer from chronic mood switches with potential severe consequences. Thus, early detection, diagnosis and initiation of correct treatment are critical. Cultured adipocytes from 35 patients with BD and 38 healthy controls were analysed using signal pathway reporter assays, that is, protein kinase C (PKC), protein kinase A (PKA), mitogen-activated protein kinases (extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK)), Myc, Wnt and p53. The levels of activated target transcriptional factors were measured in adipocytes before and after stimulation with lithium and escitalopram. Variations were analysed in the loci of 25 different single-nucleotide polymorphisms (SNPs). Activation of intracellular signals in several pathways analysed were significantly higher in patients than in healthy controls upon drug stimulation, especially with escitalopram stimulation of PKC, JNK and Myc, as well as lithium-stimulated PKC, whereas no meaningful difference was observed before stimulation. Univariate analyses of contingency tables for 80 categorical SNP results versus diagnoses showed a significant link with the ANK3 gene (rs10761482; likelihood ratio χ(2)=4.63; P=0.031). In a multivariate ordinal logistic fit for diagnosis, a backward stepwise procedure selected ANK3 as the remaining significant predictor. Comparison of the escitalopram-stimulated PKC activity and the ANK3 genotype showed them to add their share of the diagnostic variance, with no interaction (15% of variance explained, P<0.002). The study is cross-sectional with no longitudinal follow-up. Cohorts are relatively small with no medication-free patients, and there are no ‘ill patient’ controls. It takes 3 to 4 weeks of culture to expand adipocytes that may change epigenetic profiles but remove the possibility of medication effects. Abnormalities in the reactivity of intracellular signal pathways to stimulation and the ANK3 genotype may be associated with pathogenesis of BD. Algorithms using biological patterns such as pathway reactivity together with structural genetic SNP data may provide opportunities for earlier detection and effective treatment of BD.
8. Gastrointestinal side effects associated with antidepressant treatments in patients with major depressive disorder: A systematic review and meta-analysis
Gastrointestinal side effects (SEs) are frequently observed in patients with major depressive disorder (MDD) while taking antidepressants and may lead to treatment discontinuation. The aim of this meta-analysis is to provide quantitative measures on short-term rates of gastrointestinal SEs in MDD patients treated with second-generation antidepressants. An electronic search of the literature was conducted by using MEDLINE, ISI Web of Science – Web of Science Core Collection, and Cochrane Library databases. Eligible studies had to focus on the use of at least one of 15 antidepressants commonly used in MDD (i.e., agomelatine, bupropion, citalopram, desvenlafaxine, duloxetine, escitalopram, fluoxetine, fluvoxamine, levomilnacipran, mirtazapine, paroxetine, reboxetine, sertraline, venlafaxine, and vortioxetine) and report data on treatment-emergent gastrointestinal SEs (i.e. nausea/vomiting, diarrhoea, constipation, abdominal pain, dyspepsia, anorexia, increased appetite and dry mouth) within 12 weeks of treatment. Overall, 304 studies were included in the meta-analyses. All the considered antidepressants showed higher rates of gastrointestinal SEs than placebo. Escitalopram and sertraline were shown to be the least tolerated antidepressants on the gastrointestinal tract, being associated with all the considered SEs with the exception of constipation and increased appetite, while mirtazapine was shown to be the antidepressant with fewer side effects on the gut, being only associated with increased appetite. In conclusion, commonly used antidepressants showed different profiles of gastrointestinal SEs, possibly related to their mechanisms of action. The specific tolerability profile of each compound should be considered by clinicians when prescribing antidepressants in order to improve adherence to treatment and increase positive outcomes in patients with MDD.