Imipramine Hydrochloride

FRIDAY, March 24, 2023 -- Endless worry, irritability and insomnia are all symptoms of a possible anxiety disorder . Luckily, there are numerous anxiety medications that can help ease the condition. Joy Alonzo , a specialist in the pharmacotherapy of mental disorders at Texas A&M's College of Pharmacy, said recently, “If you understand the different types of medication, then you can become a better advocate for your anxiety treatment. Anxiety is one of the most under-treated mental illnesses, and we need to talk more about it.” So, what medications can bring relief from crippling anxiety? According to the Anxiety & Depression Association of America (ADAA), the most common classes of drugs for the treatment of anxiety include: Selective serotonin reuptake inhibitors (SSRIs) Serotonin-norepinephrine reuptake inhibitors (SNRIs) Benzodiazepines Tricyclic antidepressants Here is a rundown on medications for anxiety. Selective serotonin reuptake i nhibitors (SSRIs) SSRIs work by preventing the body from reabsorbing serotonin, which leaves more available for use. The ADAA describes serotonin as a neurotransmitter that plays a role in feelings of well-being and happiness. SSRIs are considered the first-line treatment for all types of anxiety disorders. A higher dose may be required when treating obsessive-compulsive disorder (OCD). Common side effects : Insomnia Sleepiness Sexual dysfunction Weight gain Dry mouth Common SSRIs: Citalopram ( Celexa ) Escitalopram ( Lexapro ) Fluoxetine ( Prozac , Sarafem ) Paroxetine ( Paxil , Paxil CR , Pexeva , Brisdelle ) Sertraline ( Zoloft ) What else you should know about SSRIs: SSRIs may make it easier to engage in psychotherapy and other wellness activities They may help improve other symptoms of anxiety, including headaches and sleep disturbances Initial side effects typically disappear after four to eight weeks SSRIs are safe for long-term use Check with your provider before stopping their use or changing your dose Serotonin-norepinephrine reuptake inhibitors (SNRIs) This class of medication is also a first-line treatment for anxiety disorders, except for OCD. It works by inhibiting the brain cells' reabsorption of both serotonin and norepinephrine. Serotonin is the neurotransmitter that helps with a sense of well-being. According to Anxiety.org , norepinephrine is considered important for its role in the body’s stress response. Common side effects: Anxiety.org states that SNRIs may have more side effects because they affect serotonin and norepinephrine. These side effects may include: Dry mouth Nausea Nervousness Insomnia Drowsiness Dizziness Headache Sexual dysfunction Loss of appetite Agitation Common SNRIs: Venlafaxine (Effexor) Desvenlafaxine ( Pristiq ) Duloxetine ( Cymbalta ) What else you should know about SNRIs Anxiety.org reports that these medications promote neuroplasticity in the brain. This may make your brain more flexible. There is evidence that these medications work best in combination with psychotherapy. But there is one important caveat. “SSRIs and SNRIs are not an instant fix for symptoms associated with an anxiety disorder, nor do they even provide immediate relief,” Alonzo said. “They work by interacting with the neurotransmitters and receptors in your brain, which can help regulate mood, sleep and energy levels. It is important for patients to understand that these medications may take four to six weeks for full effect.” Benzodiazepines Benzodiazepines are considered a second-line therapy for the treatment of generalized anxiety disorder. According to the ADAA, they work by strengthening the GABA neurotransmitter. This neurotransmitter plays a primary role in feeling calm, muscle relaxation, reduction in brain activity and sleep. Most common side effects: Drowsiness Confusion Dizziness Depression Impaired coordination Vision problems Common benzodiazepines: Alprazolam ( Xanax ) Lorazepam ( Ativan ) Diazepam ( Valium ) What else you should know about benzodiazepines for the treatment of anxiety: They act quickly, but do not stay in the system for long They are not safe for continuous use, and can be addictive May be initiated with a first-line treatment, and then tapered off Do not operate heavy equipment while taking Do not mix with alcohol Not recommended for people with suicidal or addictive tendencies Tricyclic antidepressants According to the Mayo Clinic , tricyclic antidepressants are among the earliest antidepressants. They are often recommended when newer drugs have not been effective. They are not typically used for social anxiety disorder or OCD. They also work by blocking the reabsorption of serotonin and norepinephrine, but their mechanism of action is different and they typically cause more side effects than newer treatments. Common tricyclic antidepressants: Imipramine (Tofranil) Nortriptyline (Pamelor) Desipramine (Norpramin) Clomipramine (Anafranil) Common side effects: Drowsiness Blurred vision Constipation Dry mouth Drop in blood pressure when going from sitting to standing Urine retention Weight loss/weight gain Excessive sweating Tremor Sexual dysfunction What else you should know about tricyclic antidepressants: You should not stop taking these medications abruptly You may need to have blood work done to determine the correct dose Disorientation can occur in older people at higher doses May cause a rapid or irregular heart rate Can increase seizure activity if prone to seizures When to seek treatment for anxiety The National Institute of Mental Health lists these as common symptoms of anxiety: Feeling restless, wound up or on edge Being easily fatigued Having difficulty concentrating Being irritable Having headaches, muscle aches, stomach aches or unexplained pains Difficulty controlling feelings of worry Having sleep problems, such as difficulty falling or staying asleep The ADAA recommends seeking medication for anxiety when you are having physical symptoms, are unable to do what you want because of how you feel or are unable to make life choices because of fear. It is never too early to start treatment. Anxiety treatment can be more effective when used with therapy. It is essential to keep all your appointments with your provider. Do not stop your medication or change the dose without discussing it with your provider. If the side effects affect your daily activities, inform your provider immediately. If, at any time, you feel as though you may be suicidal, reach out to your provider or go to the nearest emergency room. You can also call or text the national suicide prevention hotline at 988. Posted March 2023

A new study has identified a combination of three existing drugs that significantly extends survival in mouse models of the lethal brain cancer glioblastoma multiforme (GBM). A Ludwig Cancer Research study has identified a combination of three existing drugs that significantly extends survival in mouse models of the lethal brain cancer glioblastoma multiforme (GBM). Researchers led by Ludwig Lausanne's Douglas Hanahan report in the current issue of Cancer Cell how the drugs used in the combination -- an antidepressant, an immune checkpoint blockade antibody and a mouse analog of a cancer therapy that by themselves provide no survival benefit against GBM -- synergize to unleash potently therapeutic immune responses against the tumor. "Our investigation illustrates the great potential of drug repurposing for cancer therapy," said Hanahan, distinguished scholar at the Ludwig Institute for Cancer Research Lausanne Branch. "We've shown here that three extensively characterized drugs already in use in the clinic can be newly combined to lift the tumor's immunosuppressive barrier and induce a therapeutic immune response that significantly extends survival in mouse models of GBM, a cancer that has so far evaded every therapy used to treat it." Hanahan and his colleagues have been exploring in preclinical studies whether drug combinations that target distinct growth-promoting properties of tumors might work synergistically to stall or reverse disease progression. Previous studies in Hanahan's lab had shown that a generic "tricyclic" antidepressant, imipramine, could be used in combination with an anticoagulant drug to hyperactivate a process known as autophagy, in which cells cannibalize their own proteins and organelles for the nutrients required to sustain their growth. Hyperactivation of autophagy by these drugs modestly extended survival of mice with GBM. In this study, the researchers tested whether a drug aimed at an unrelated phenomenon, the abnormal blood vessels of tumors, used in combination with imipramine might further improve outcomes. They used a mouse analog of the human anti-VEGF antibody bevacizumab, which has been approved as a second line treatment for GBM, though not so much to extend survival as to provide relief to patients by alleviating the edema caused by the aberrant vasculature. Bevacizumab is known to quasi-normalize leaky tumor blood vessels, whose abnormalities also compromise both chemotherapy and immunotherapy. The researchers found that combining imipramine and the VEGF-blocking antibody significantly delayed tumor progression and increased survival times in mice with GBM. The combination, they discovered, disrupts the immune defenses of the tumor via multiple mechanisms, unleashing a powerful anti-tumor immune response characterized by the recruitment of both helper and cytotoxic T cells, which are critical to anti-tumor immunity. An analog of human-specific bevacizumab that targets the VEGF angiogenic factor in mice proved to remodel the tumor blood vessels in ways that are known to promote the infiltration of T cells. At the same time, imipramine's hyperactivation of autophagy stimulated anti-tumor immunity. But that wasn't all. Hanahan and his team found that the antidepressant also has a separate and unanticipated effect on a type of immune cell known as the macrophage, which is found in large numbers in GBM tumors. Imipramine, it turns out, also targets a biochemical signaling pathway that helps maintain macrophages in a so-called "M2" state, in which they support tumor growth. Blocking that signal with the antidepressant reprogrammed them into an "M1" state that supports infiltration and killing of cancer cells by T cells. Yet though this drug combination extended survival, its effects were not very durable. Hanahan and his team, however, saw an opportunity in its reconditioning of the tumor's immune microenvironment. To capitalize on that opportunity, they added to the mix a checkpoint blockade antibody that amplifies anti-tumor immune responses. Such treatments have so far failed dismally against GBM in humans. But when added to the bevacizumab-imipramine combination, an ant-PD-L1 antibody drug significantly extended the survival of the mice. "Because each of these therapies are already in clinical use," said Hanahan, "they wouldn't have to go through the time-consuming pharmacological development and safety testing required of novel drugs. For this reason, we are hopeful that the combination therapy we've identified in this study can be tested relatively soon in human clinical trials for GBM, a fiercely aggressive cancer for which there is a desperate need for new treatment strategies." Indeed, planning is already underway for a phase I pilot trial to evaluate the drug combination. If it wins regulatory approval, the trial will be led by Hanahan and Andreas Hottinger of the Centre Hospitalier Universitaire Vaudois in Lausanne. This study was supported by Ludwig Cancer Research, the European Research Council, the Swiss Federal Institute of Technology Lausanne (EPFL), Barrow Neurological Institute, Fondation Sante, the Swiss Cancer Research Foundation and the Netherlands Organization for Scientific Research. Hanahan is also an Emeritus Professor and Former Director of the Swiss Institute for Experimental Cancer Research (ISREC) within the Swiss Federal Institute of Technology Lausanne (EPFL).