Latest news with #sertraline
Medscape
2 days ago
- Health
- Medscape
FDA Panel Rejects Combo Drug for PTSD
An FDA advisory panel has resoundingly rejected the supplemental new drug application for the atypical antipsychotic brexpiprazole (Rexulti, Otsuka Pharmaceutical Co., Ltd.), in combination with the selective serotonin reuptake inhibitor (SSRI) sertraline, for the treatment of adults with posttraumatic stress disorder (PTSD). Based on the data at hand, in a 10 to 1 vote, the Psychopharmacologic Drugs Advisory Committee felt that the efficacy of brexpiprazole, when started concurrently with sertraline, has not been established in PTSD. In a briefing document released ahead of the FDA committee meeting, FDA reviewers flagged 'discordant' results from the two phase 3 trials. They noted that while study '071' was 'robustly positive,' study '072' was 'clearly and convincingly' negative and failed to demonstrate statistical significance on its primary or secondary endpoints. Given the conflicting phase 3 results, the company also provided the FDA with data from the '061' phase 2 study. However, the reviewers cited statistical and methodologic concerns with this study. The data from this study were 'retrospectively analyzed with post hoc multiplicity control methods to provide additional efficacy evidence, raising concerns about type I error inflation,' the reviewers cautioned. The committee also had concerns about the 061 data analysis. Taken together, the data 'is not crossing that bar in my head,' said committee member Jess Fiedorowicz, MD, PhD, head of the Department of Mental Health, The Ottawa Hospital, Ottawa, Ontario, Canada. Walter Dunn, MD, PhD, director, Mood Disorders Section, West Los Angeles Veterans Affairs Medical Center, Los Angeles, agreed. Dunn said while he is a 'strong advocate' for increasing treatment options for PTSD, he was 'not convinced' of the efficacy of the combination given the conflicting data. Murray Raskind, MD, professor, Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle, felt it would be 'hard to translate the confusing contradictory datasets to my clinical practice.' Raskind also said he is not convinced the combination offers clinicians a new tool. Brexpiprazole is currently approved as adjunctive treatment of major depressive disorder in adults, treatment of schizophrenia in adults and adolescents aged 13 years or older, and treatment of agitation associated with Alzheimer's dementia. 'We already have sertraline, and we already have brexpiprazole. The prescribing physician can make the decision to progress to the combination or start with it in the patient with PTSD,' Raskind said. Other committee members agreed. Committee members in general felt that in the real world, co-initiation of both drugs may not be the preferred approach. It's more likely that clinicians would opt to start sertraline first, then add brexpiprazole if needed. 'Third-party payers may require that,' Dunn predicted. During the public comment period, Michael Abrams, PhD, MPH, senior health researcher with Public Citizen, said the data supporting the use of this combination for treatment of PTSD is 'weak at best, based on two conflicting phase 3 trials and a questionable post hoc analysis of data from a phase 2 trial,' and he urged the committee and the FDA to reject the combination. The lone 'yes' vote for the brexpiprazole-sertraline combination in PTSD came from the patient advocate on the committee, Laura Block, PharmD, clinical pharmacist (retired), Cary, North Carolina. Block noted that while both of these individual component drugs are on the market, a third-party payer isn't likely to pay without an FDA-approved indication. 'That means that there are those who are going to have difficulty accessing,' Block commented. At the same time, Block said she would not want to offer patients 'destructive false hope,' and whether it is approved, she would like to see either a phase 3 or phase 4 study. Currently, the SSRI sertraline and paroxetine are the only FDA-approved medications for PTSD, and while these medications can be effective, many patients fail to achieve remission or discontinue treatment due to side effects or lack of response. The proposed upfront co-initiation of brexpiprazole with sertraline is a novel treatment paradigm. If approved by the FDA, it would be the first new treatment for PTSD in more than 20 years. The FDA is not required to follow the advice of its advisory committees, but it often does.
Medscape
14-07-2025
- Health
- Medscape
First New PTSD Drug in Two Decades On the Horizon?
The Psychopharmacologic Drugs Advisory Committee of the FDA is set to meet on July 18 to consider a supplemental new drug application for brexpiprazole (Rexulti, Otsuka Pharmaceutical Co., Ltd.), in combination with sertraline, for the treatment of adults with posttraumatic stress disorder (PTSD). If approved, it would be the first new treatment for PTSD in more than 20 years. 'It is my hope that the FDA does approve this treatment for two related reasons — the data look positive and compelling, and there's a tremendous unmet need in PTSD,' Roger McIntyre, MD, professor of psychiatry and pharmacology and head of the Mood Disorders Psychopharmacology Unit, University of Toronto, Toronto, Ontario, Canada, told Medscape Medical News. What's in the Treatment Toolbox Now? PTSD is a 'common, severe, and nonremitting condition,' McIntyre noted. According to the National Center for PTSD, the condition affects roughly 13 million adults in the US in any given year. This represents about 5% of the adult population. PTSD can develop following exposure to traumatic events such as combat, assault, disasters, or severe accidents. Core symptoms of PTSD include intrusive memories and flashbacks, avoidance behaviors, negative alterations in mood and cognition, and hyperarousal. Currently, the selective serotonin reuptake inhibitors (SSRI), sertraline and paroxetine, are the only FDA-approved medications for PTSD, and while these medications can be effective, many patients fail to achieve remission or discontinue treatment due to side effects or lack of response. Other medications used off-label to treat PTSD — including prazosin, mirtazapine, atypical antipsychotics, and mood stabilizers — have shown variable efficacy. There has not been a new FDA-approved drug for PTSD in over two decades, underscoring the need for better therapeutic options, particularly for patients who do not fully respond to SSRI alone. Why Brexpiprazole Plus Sertraline? Brexpiprazole is an atypical antipsychotic currently approved as adjunctive treatment of major depressive disorder (MDD) in adults; treatment of schizophrenia in adults and adolescents aged 13 years or older; and treatment of agitation associated with Alzheimer's dementia. The combination of brexpiprazole and sertraline could address the limitations of SSRI alone by working synergistically to treat PTSD. Sertraline increases serotonin levels in the brain to improve mood and reduce anxiety. Brexpiprazole has a complex mechanism of action involving multiple neurotransmitter systems, including but not limited to serotonin and dopamine. Together, they may target different aspects of PTSD, potentially leading to a more comprehensive reduction in symptoms. What Do the Phase 3 Data Show? In a pivotal, double-blind, randomized controlled, phase 3 trial, brexpiprazole plus sertraline provided significantly greater relief of PTSD symptoms than sertraline plus placebo. The results were published late last year in JAMA Psychiatry and reported by Medscape Medical News at that time. The trial enrolled 416 adults (mean age, 37 years; 75% women) aged 18-65 years with a Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition ( DSM-5 ) diagnosis of PTSD and symptoms for at least 6 months prior to screening. At baseline, participants had a mean Clinician Administered PTSD Scale (CAPS-5) for DSM-5 total score of 38.4, indicating moderate to high severity PTSD. The average time from the index traumatic event was 4 years, and three fourths had no prior exposure to PTSD prescription medications. Participants underwent a 1-week placebo run-in period followed by randomization to daily oral brexpiprazole 2-3 mg plus sertraline 150 mg or daily sertraline 150 mg plus placebo for 11 weeks. At week 10, brexpiprazole plus sertraline demonstrated statistically significant greater improvement in the CAPS-5 total score (primary outcome) than sertraline plus placebo (mean change, -19.2 points vs -13.6 points; P < .001). Brexpiprazole plus sertraline also led to statistically significant greater improvement on all key secondary and other efficacy endpoints, both clinician-reported and patient-reported, including measures of anxiety, depression, intrusive symptoms, hyperarousal, and overall functioning. Combining an atypical antipsychotic with an antidepressant for PTSD 'builds on what we've been doing in depression,' Elspeth Ritchie, MD, chair of Psychiatry, MedStar Washington Hospital Center, Washington, DC, noted in an interview with Medscape Medical News . 'We have found that a combination of a low-dose antipsychotic and an antidepressant is helpful for depression, so it makes sense that it will be helpful for PTSD. However, this has been mostly based on clinical decisions, without a heavy research background. Good science is always helpful to support those clinical decisions,' Ritchie told Medscape Medical News . What About Safety? In the phase 3 trial, brexpiprazole plus sertraline had a safety profile consistent with that of brexpiprazole in approved indications. The rate of discontinuation due to adverse events was low (3.9% for brexpiprazole plus sertraline vs 10.2% for sertraline plus placebo), indicating that most participants tolerated the brexpiprazole and sertraline combination treatment, the study team said. In both treatment groups, the only treatment-emergent adverse event (TEAE) with incidence greater than 10% was nausea, a known adverse effect of sertraline treatment. Weight gain was greater in participants receiving the combination. At the last visit, a weight gain of 7% or greater from week 1 was experienced by 8% of participants taking brexpiprazole with the sertraline group and 5% of those taking the sertraline plus placebo. Previous analyses in schizophrenia and MDD show that brexpiprazole is associated with moderate weight gain (+3 to 4 kg over 1 year). The incidence of sedating TEAEs (a concern with some antipsychotics) was generally low, although fatigue (7% vs 4%) and somnolence (5% vs 3%) were more common with brexpiprazole plus sertraline than with sertraline alone. There were no clinically meaningful between-group differences in changes in laboratory test parameters, vital signs, or ECG and participant-reported TEAEs related to suicidality. Potential Concerns As with any new drug application, several questions and issues are likely to be raised by the advisory committee. They could include whether the clinical benefit is substantial enough to warrant approval and how the observed effect sizes compare to existing approved therapies and evidence-based psychotherapies. McIntyre told Medscape Medical News what's particularly noteworthy is that the magnitude of the improvement in PTSD symptoms with brexpiprazole plus sertraline is greater than with sertraline alone. 'That's a very important statement. And this high level of efficacy was consistent on the secondary outcome measures, and the overall tolerability and safety seemed very acceptable,' he said. What's equally important, said McIntyre, is that most people with PTSD have depression and anxiety, and the brexpiprazole plus sertraline combination was more helpful than sertraline alone on the measures of anxiety and depression. 'This is really important, especially in light of the fact that this medication [brexpiprazole] is already approved for adults living with major depressive disorder and inadequate response to antidepressants,' McIntyre said. McIntyre added he suspects some questions the committee may have could relate to the extent to which it's the case that brexpiprazole is effective in PTSD regardless of the antidepressant that is prescribed with it. 'There also will be the inevitable questions about the absence of long-term data which I think will need to be addressed given how chronic and relapse prone this condition is,' McIntyre said. The committee may ask how trauma and PTSD will be screened in primary care and how outcomes related to this therapy will be evaluated in everyday clinical practice, McIntyre said. Overall, McIntyre said brexpiprazole plus sertraline in PTSD is a 'very positive' development for the field. 'PTSD is a terrible condition. It's so darn common, and we just don't have enough treatments for it. The data look good for my perspective. My fingers are crossed for the patients with PTSD and their families,' said McIntyre.
Medical News Today
14-05-2025
- Health
- Medical News Today
Phentermine interactions: Other medications, alcohol, and more
Phentermine has possible interactions with alcohol, some other drugs, and certain supplements. Examples include sertraline, methylphenidate, and metoprolol. Talk with your doctor to avoid potentially harmful effects from phentermine interactions. Phentermine is a generic drug used to help with weight loss in certain adults who have overweight or obesity. It is prescribed for short-term use (a few weeks) alongside diet and exercise. An interaction occurs when one substance causes another substance to have a different effect than expected. Phentermine comes in two different forms: oral tablets and oral capsules. Both forms have the same interactions. By learning about possible phentermine interactions, you can work with your doctor to ensure phentermine will be safe and effective for you to take. For additional information about phentermine, including details about its uses, see this phentermine overview article. Before you start treatment with phentermine, tell your doctor and pharmacist about any prescription, over-the-counter, and other medications you take. By sharing this information with them, you may help prevent possible interactions. To learn whether phentermine interacts with supplements, herbs, or vitamins, see the 'Phentermine and other interactions' section. If you have questions about drug interactions that may affect you, ask your doctor or pharmacist. Here's a table of drugs that can interact with phentermine. Keep in mind this table doesn't include all drugs that may interact with phentermine. Some of these interactions are described in detail in 'Drug interactions in depth.' In some cases, factors or conditions could prevent your doctor from prescribing phentermine due to the risk of harm. These are known as contraindications. Below are the contraindications of phentermine. Note: Before you start treatment with phentermine, it's important to tell your doctor if these contraindications apply to you. They can determine whether to prescribe phentermine. Doctors typically won't prescribe phentermine for people with heart disease, including congestive heart failure, arrhythmias (irregular heartbeat), or unmanaged hypertension (high blood pressure). This is because phentermine may cause a serious increase in your blood pressure. This can put additional strain on your heart, which may worsen existing heart disease. If you have any heart problems, talk with your doctor before taking phentermine. They'll likely prescribe a safer treatment option for weight loss. Doctors typically won't prescribe phentermine for people with hyperthyroidism (an overactive thyroid). This is because taking phentermine can make symptoms of hyperthyroidism worse, such as increased heart rate, hyperactivity, and excessive sweating. If you have hyperthyroidism, talk with your doctor before taking phentermine. They'll likely prescribe a treatment other than phentermine for weight loss. Doctors typically won't prescribe phentermine for people with glaucoma. This is because phentermine can further increase the pressure in your eye and worsen your glaucoma. Worsening glaucoma can lead to permanent damage to your vision. If you have glaucoma, talk with your doctor before taking phentermine. They'll likely suggest an alternative medication that is safer for you. Doctors typically won't prescribe phentermine for people with agitation. Phentermine is a stimulant and can cause nervousness, irritability, insomnia (trouble sleeping), or a racing heart. If you're already feeling very nervous, anxious, restless, or agitated, phentermine can worsen those feelings. If you're feeling agitated, anxious, or overwhelmed, talk with your doctor before taking phentermine. They may recommend treating the anxiety first, or they might suggest a different, safer approach to weight loss that won't affect your mood or mental state. This is because taking phentermine with an MAOI can increase your blood pressure and lead to a hypertensive crisis (a dangerous increase in blood pressure). This is because MAOIs block the breakdown of certain brain chemicals like norepinephrine, which controls blood pressure. Phentermine increases the release of norepinephrine. So, when both are taken together, norepinephrine can build up, causing your blood pressure to rise. MAOIs that can interact with phentermine include: linezolid (Zyvox) phenelzine (Nardil) selegiline (Emsam) isocarboxazid (Marplan) Before you start treatment with phentermine, it's important to tell your doctor if you take an MAOI. They'll likely have you stop taking the MAOI and wait at least 2 weeks before starting treatment with phentermine. Likewise, after you stop taking phentermine, your doctor will typically have you wait at least 2 weeks before starting treatment with an MAOI. Doctors typically won't prescribe phentermine during pregnancy. If you're able to become pregnant, they'll likely recommend using an effective birth control before prescribing phentermine. This is because phentermine may not be safe to take during pregnancy. Weight loss isn't recommended during pregnancy, even if you already have overweight or obesity. In addition, phentermine has not been studied in females. And it isn't known if taking phentermine can cause fetal harm, such as congenital anomalies, commonly known as birth defects, or pregnancy loss. Doctors typically won't prescribe phentermine for people who have a history of drug misuse (also known as 'abuse'). Phentermine is a type of stimulant medication that's similar to amphetamines. Because of how it affects the brain, there's a risk that it can become habit-forming. If you have a history of drug misuse, talk with your doctor before taking phentermine. You can ask them about other treatments that may be better for you. If you've had an allergic reaction to phentermine or any of its ingredients, your doctor will likely not prescribe phentermine. Taking the drug could cause another allergic reaction. You can ask them about other treatments that may be better choices for you. There are no known interactions between phentermine and alcohol. However, if you drink alcohol, your doctor may advise you to avoid or limit it during phentermine treatment. This is because drinking alcohol while taking the drug may worsen some of phentermine side effects. For example, you may experience: headache dizziness diarrhea dry mouth If you consume alcohol during phentermine treatment, these side effects may be more likely to occur. If you have questions about drinking alcohol while taking phentermine, talk with your doctor. Here's a closer look at certain drug interactions of phentermine. Taking phentermine with diabetes medications can raise the risk of low blood sugar, especially if you're taking insulin or drugs that increase insulin release (like sulfonylureas). This happens because by reducing appetite, phentermine may lead to decreased food intake, which can lower blood sugar levels. Here are some diabetes drugs that may interact with phentermine: insulin (Lantus, Humalog, Levemir, others) glyburide (Diabeta) glipizide (Glucotrol) empagliflozin (Jardiance) rosiglitazone (Avandia) exenatide (Byetta, Bydureon) Tell your doctor if you're taking any medications for diabetes before starting treatment with phentermine. Your doctor will likely want to monitor your blood sugars more closely. They may need to adjust your diabetes medication if your blood sugars are too low. Taking phentermine with other stimulant medications can greatly increase the risk of serious side effects. These side effects include high blood pressure, rapid heart rate, anxiety, insomnia, and, in severe cases, heart attack or stroke. This is because these medications have similar effects on the body. So taking stimulants can further worsen the side effects of phentermine. Here are some other stimulant medications that may interact with phentermine: amphetamine/ dexamphetamine (Adderall) lisdexamfetamine (Vyvanse) methylphenidate (Ritalin, Concerta, others) Tell your doctor if you're taking a stimulant medication before starting phentermine. If you're taking a stimulant, your doctor will want to take extra steps to keep you safe, such as closely monitoring your blood pressure or adjusting the dose or timing of your medications. Or your doctor might recommend a different weight loss medication that doesn't have stimulant effects if they feel it would be safer for you. Taking phentermine with SSRIs may increase the risk of serotonin syndrome. Both phentermine and SSRIs affect serotonin in the brain. Taking them together can cause serotonin levels to get too high, leading to serotonin syndrome. Here are some SSRIs that may interact with phentermine: sertraline (Zoloft) paroxetine (Paxil) fluoxetine (Prozac) citalopram (Celexa) If you're taking an SSRI with phentermine, your doctor will monitor you closely for side effects. Tell your doctor right away if you notice symptoms like agitation, confusion, fast heartbeat, high blood pressure, or tremors. Phentermine may have other interactions, such as with supplements, foods, vaccines, or lab tests. Here are some potential interactions with phentermine. Keep in mind that the following information does not include all other possible phentermine interactions. Before you start treatment with phentermine, tell your doctor and pharmacist about any supplements, herbs, and vitamins you take. By sharing this information with them, you may help prevent possible interactions. If you have questions about drug interactions that may affect you, ask your doctor or pharmacist. Doctors will typically recommend you avoid taking St. John's wort with phentermine. St. John's wort is an herbal supplement that may be used to treat depression and other conditions. Both phentermine and St. John's wort can increase serotonin levels in the brain. Using them together could cause a higher level of serotonin, leading to an increased risk of serotonin syndrome. Symptoms of serotonin syndrome may include confusion, agitation, rapid heart rate, high blood pressure, tremors, and fever. Your doctor may be able to suggest a treatment option other than St. John's wort. There are no specific reports of vitamins interacting with phentermine. However, that doesn't mean vitamin interactions won't occur or be recognized in the future. Because of this, you should talk with your doctor or pharmacist before taking any vitamin product with phentermine. Phentermine may interact with caffeine. Consuming too much caffeine while taking phentermine can increase the risk of side effects of phentermine, including nervousness, headaches, or insomnia. Foods and beverages that contain caffeine include: coffee tea chocolate energy drinks Because of this interaction, your doctor will likely recommend limiting how much caffeine you consume during phentermine treatment. If you'd like to learn more about eating certain foods during treatment with phentermine, talk with your doctor. There aren't any known interactions between phentermine and vaccines. Talk with your doctor or pharmacist to check whether you're due for any vaccines. Phentermine isn't known to interact with lab tests. If you have concerns about this medication interacting with lab tests, talk with your doctor. PHENTERMINE INTERACTION WITH CANNABIS OR CBD Cannabis (often called marijuana) and cannabis products, such as cannabidiol (CBD), have not been specifically reported to interact with phentermine. However, as with any drug or supplement, talk with your doctor before using cannabis in combination with phentermine. The impact of cannabis may affect how well you stick to your phentermine treatment plan. Note: Cannabis is illegal at a federal level but is legal in many states to varying degrees. Certain medical conditions and other factors may increase the risk of interactions with phentermine. Before you take this drug, be sure to talk with your doctor about your health history. Phentermine may not be the right treatment option if you have certain medical conditions or other factors affecting your health. Health conditions or factors that might interact with phentermine include: High blood pressure: Phentermine can cause your blood pressure to increase. If you have high blood pressure, phentermine may further increase it or make it harder to manage. Your doctor will monitor your blood pressure more closely while you're taking phentermine. Phentermine can cause your blood pressure to increase. If you have high blood pressure, phentermine may further increase it or make it harder to manage. Your doctor will monitor your blood pressure more closely while you're taking phentermine. Diabetes: Because phentermine reduces how much you eat, it can sometimes cause your blood sugar to go down. As a result, your doctor may need to lower the dose of your diabetes medication. Because phentermine reduces how much you eat, it can sometimes cause your blood sugar to go down. As a result, your doctor may need to lower the dose of your diabetes medication. Allergic reaction: If you've had an allergic reaction to phentermine or any of its ingredients, your doctor will likely not prescribe phentermine. Taking the drug could cause another allergic reaction. You can ask them about other treatments that may be a better option for you. If you've had an allergic reaction to phentermine or any of its ingredients, your doctor will likely not prescribe phentermine. Taking the drug could cause another allergic reaction. You can ask them about other treatments that may be a better option for you. Breastfeeding: It's not recommended to breastfeed a child while taking phentermine. There isn't enough information to determine whether the drug passes into breast milk or what effects phentermine may have on a child who is breastfed. If you're breastfeeding or planning to, talk with your doctor before taking phentermine. They can talk with you about treatment options and ways to feed a child other than breastfeeding. It's not recommended to breastfeed a child while taking phentermine. There isn't enough information to determine whether the drug passes into breast milk or what effects phentermine may have on a child who is breastfed. If you're breastfeeding or planning to, talk with your doctor before taking phentermine. They can talk with you about treatment options and ways to feed a child other than breastfeeding. Pregnancy: There haven't been enough clinical trials to determine whether phentermine is safe to take while pregnant. If you're pregnant or planning to become pregnant, tell your doctor before starting phentermine. They can advise you on the right treatment plan for you. Here are some frequently asked questions about phentermine and possible interactions. Yes, you can usually take phentermine and antibiotics (like amoxicillin or cephalexin) together safely. However, even if there's no drug interaction, taking antibiotics while on phentermine might increase your chances of experiencing side effects, especially if you're not eating or drinking enough. Talk with your doctor or pharmacist if you have questions about taking antibiotics during treatment with phentermine. Yes, it's generally safe to take phentermine with high blood pressure medications. However, phentermine is a stimulant that can raise your heart rate and blood pressure. If your blood pressure is well managed with medication, your doctor may decide that it's safe for you to take phentermine. They'll likely monitor you closely and may start you on a lower dose. Or they may recommend a different weight loss medication that's safer for you. If your blood pressure is unmanaged or if you have a history of heart problems, stroke, or arrhythmias, your doctor likely won't prescribe phentermine. This is due to the increased risk of serious side effects. If you have high blood pressure, talk with your doctor before starting phentermine. They can decide whether phentermine is a safe treatment option for you. You can take certain steps to help prevent interactions with phentermine. Your doctor and pharmacist are key resources, so reach out to them before starting treatment. For example, you should plan to do the following: Let them know if you drink alcohol or use cannabis. Tell them about any other medications you take, as well as any supplements, herbs, and vitamins. Create a medication list , which your doctor and pharmacist can help you fill out. It's also important to read the phentermine label and other paperwork that may come with the drug. The label may have colored stickers that mention an interaction. The paperwork, sometimes called the medication guide or patient package insert, may contain details about interactions. If phentermine doesn't come with paperwork, you can ask your pharmacist to print a copy. If you need help reading or understanding this information, ask your doctor or pharmacist. You can also help prevent interactions with phentermine by taking it exactly as your doctor prescribes. Disclaimer: Medical News Today has made every effort to make certain that all information is factually correct, comprehensive, and up to date. However, this article should not be used as a substitute for the knowledge and expertise of a licensed healthcare professional. You should always consult your doctor or another healthcare professional before taking any medication. The drug information contained herein is subject to change and is not intended to cover all possible uses, directions, precautions, warnings, drug interactions, allergic reactions, or adverse effects. The absence of warnings or other information for a given drug does not indicate that the drug or drug combination is safe, effective, or appropriate for all patients or all specific uses. Obesity / Weight Loss / Fitness Pharmacy / Pharmacist Drugs
