144-407: Pregabalin , sold under the brand name Lyrica among others, is an anticonvulsant , analgesic , and anxiolytic amino acid medication used to treat epilepsy , neuropathic pain , fibromyalgia , restless legs syndrome , opioid withdrawal , and generalized anxiety disorder (GAD). Pregabalin also has antiallodynic properties. Its use in epilepsy is as an add-on therapy for partial seizures . It
288-643: A "high" similar to marijuana with the use of pregabalin; there is a potential for developing dependence on these substances, and withdrawal symptoms may occur if the medication is abruptly discontinued. It is a Class C controlled substance in the UK. Therefore, pregabalin requires a prescription. Furthermore, the prescription must clearly set forth the dose. Pregabalin has potential for misuse. It can bring about an elevated mood in users. It can also have serious side effects, particularly when used in combination with other drugs. For drug-resistant focal epilepsy, pregabalin
432-462: A black box warning for suicidal ideation, but it is generally considered that the risk of suicide in untreated depression is far higher than the risk of suicide when depression is properly treated. Pregabalin (Lyrica) is effective for treating GAD. It acts on the voltage-dependent calcium channel to decrease the release of neurotransmitters such as glutamate, norepinephrine and substance P . Its therapeutic effect appears after 1 week of use and
576-479: A class of drugs with hypnotic , anxiolytic , anticonvulsive, amnestic and muscle relaxant properties. Benzodiazepines act as a central nervous system depressant. The relative strength of each of these properties in any given benzodiazepine varies greatly and influences the indications for which it is prescribed. Long-term use can be problematic due to the development of tolerance to the anticonvulsant effects and dependency . Of many drugs in this class, only
720-418: A comparison of a CAM against a known drug after which no difference in subjects is found by investigators and which is used to suggest an equivalence between a CAM and a drug. Because this equates a lack of evidence with the positive assertion of efficacy, a "lack of difference" assertion is not a proper claim for efficacy. Moreover, an absence of strict definitions and standards for CAM compounds further burdens
864-427: A diverse group of pharmacological agents used in the treatment of epileptic seizures . Anticonvulsants are also increasingly being used in the treatment of bipolar disorder and borderline personality disorder , since many seem to act as mood stabilizers , and for the treatment of neuropathic pain . Anticonvulsants suppress the excessive rapid firing of neurons during seizures. Anticonvulsants also prevent
1008-431: A fasted state and 3.2 hours in a fed state (5-fold difference), and the C max is reduced by 25–31% in a fed versus fasted state. Pregabalin crosses the blood–brain barrier and enters the central nervous system . However, due to its low lipophilicity , pregabalin requires active transport across the blood–brain barrier. The LAT1 is highly expressed at the blood–brain barrier and transports pregabalin across into
1152-673: A few are used to treat epilepsy: The following benzodiazepines are used to treat status epilepticus : Nitrazepam , temazepam , and especially nimetazepam are powerful anticonvulsant agents, however their use is rare due to an increased incidence of side effects and strong sedative and motor-impairing properties. The following are carboxamides: The following are fatty-acids: Vigabatrin and progabide are also analogs of GABA. Gabapentinoids are used in epilepsy , neuropathic pain , fibromyalgia , restless leg syndrome , opioid withdrawal and generalized anxiety disorder (GAD). Gabapentinoids block voltage-gated calcium channels , mainly
1296-528: A formal diagnosis of GAD. Individuals with GAD often have other disorders including other psychiatric disorders (e.g., major depressive disorder ), substance use disorder, obesity, and may have a history of trauma or family with GAD. Clinicians use screening tools such as the GAD-7 and GAD-2 questionnaires to determine if individuals may have GAD and warrant formal evaluation for the disorder. Additionally, sometimes screening tools may enable clinicians to evaluate
1440-629: A greater number of minor stress-related events in life and that the number of stress-related events may be important in development of GAD (irrespective of other individual characteristics). Studies of possible genetic contributions to the development of GAD have examined relationships between genes implicated in brain structures involved in identifying potential threats (e.g., in the amygdala ) and also implicated in neurotransmitters and neurotransmitter receptors known to be involved in anxiety disorders. More specifically, genes studied for their relationship to development of GAD or demonstrated to have had
1584-446: A hereditary basis for GAD, but the exact nature of this hereditary basis is not fully understood. While investigators have identified several genetic loci that are regions of interest for further study, there is no singular gene or set of genes that have been identified as causing GAD. Nevertheless, genetic factors may play a role in determining whether an individual is at greater risk for developing GAD, structural changes in
SECTION 10
#17328012926031728-444: A larger number obtain moderate benefit. It is given equal weight as gabapentin and tricyclic antidepressants as a first-line agent, however the latter are less expensive as of 2010. Pregabalin is as effective at relieving pain as duloxetine and amitriptyline . Combination treatment of pregabalin and amitriptyline or duloxetine offers additional pain relief for people whose pain is not adequately controlled with one medication, and
1872-423: A low potential for misuse and dependency and may be preferred over the benzodiazepines for these reasons. The anxiolytic effects of pregabalin appear to persist for at least six months continuous use, suggesting tolerance is less of a concern; this gives pregabalin an advantage over certain anxiolytic medications such as benzodiazepines. Gabapentin (Neurontin), a closely related medication to pregabalin with
2016-585: A lower risk of withdrawal compared to SNRIs. If sertraline is found to be ineffective, then it is recommended to try another SSRI or SNRI. Common side effects include nausea , sexual dysfunction , headache , diarrhea , constipation , restlessness , increased risk of suicide in young adults and adolescents, among others . Sexual side effects, weight gain, and higher risk of withdrawal are more common in paroxetine than escitalopram and sertraline. In older populations or those taking concomitant medications that increase risk of bleeding, SSRIs may further increase
2160-563: A mainstay in treating GAD in adults. First-line medications from any drug category often include those that have been approved by the Food and Drug Administration (FDA) or other similar regulatory body such as the EMA or TGA for treating GAD because these drugs have been shown to be safe and effective. FDA-approved medications for treating GAD include: While certain medications are not specifically FDA approved for treatment of GAD, there are
2304-510: A meta-analysis of 39 studies comprising 21,736 subjects that found a small-to-medium association between smartphone use and anxiety. In December 2018, Frontiers in Psychiatry published a systematic review of 9 studies published after 2014 investigating associations between problematic social networking sites (SNS) use and comorbid psychiatric disorders that found a positive association between problematic SNS use and anxiety. In March 2019,
2448-577: A number of medications that historically have been used or studied for treating GAD. Other medications that have been used or evaluated for treating GAD include: Pharmaceutical treatments for GAD include selective serotonin reuptake inhibitors (SSRIs). SSRIs increase serotonin levels through inhibition of serotonin reuptake receptors. FDA approved SSRIs used for this purpose include escitalopram and paroxetine . However, guidelines suggest using sertraline first due to its cost-effectiveness compared to other SSRIs used for generalized anxiety disorder and
2592-415: A number of widely used ones (including lamotrigine and levetiracetam) carried a low risk of adverse neurodevelopmental outcomes (cognitive and behavioral) in children when compared to children born to mothers without epilepsy and children born to mothers taking other anti-seizure medications. Data from several pregnancy registries showed that children exposed to levetiracetam or lamotrigine during pregnancy had
2736-458: A real-life situation), which has greater effectiveness than imaginal exposure in regards to generalized anxiety disorder. The aim of in vivo exposure treatment is to promote emotional regulation using systematic and controlled therapeutic exposure to traumatic stimuli. Exposure is used to promote fear tolerance. Exposure therapy is also a preferred method for children who struggle with anxiety. Medications that have been studied were reviewed in
2880-798: A recent network meta-analysis that compared all studied medications with placebo and also with each other and another compared the rates of remission between different medications. Benzodiazepines (BZs) have been used to treat anxiety starting in the 1960s. There is a risk of dependence and tolerance to benzodiazepines. BZs have a number of effects that make them a good option for treating anxiety including anxiolytic, hypnotic (induce sleep), myorelaxant (relax muscles), anticonvulsant, and amnestic (impair short-term memory) properties. While BZs work well to alleviate anxiety shortly after administration, they are also known for their ability to promote dependence and are frequently used recreationally or non-medically. Antidepressants (e.g., SSRIs / SNRIs ) have become
3024-539: A relationship between gabapentinoids given before surgery and respiratory depression occurring after different kinds of surgeries. The FDA also reviewed several animal studies that showed pregabalin alone and pregabalin plus opioids can depress respiratory function. An overdose of pregabalin usually consists of severe drowsiness , severe ataxia , blurred vision , macular detachment, slurred speech , severe uncontrollable jerking motions ( myoclonus ), tonic–clonic seizures , and anxiety. Despite these symptoms an overdose
SECTION 20
#17328012926033168-506: A relationship to treatment response include: In April 2018, the International Journal of Environmental Research and Public Health published a systematic review of 24 studies researching associations between internet gaming disorder (IGD) and various psychopathologies that found a 92% correlation between IGD and anxiety and a 75% correlation between IGD and social anxiety. In August 2018, Wiley Stress & Health published
3312-423: A significant positive association between social anxiety and mobile phone addiction. In August 2022, the International Journal of Environmental Research and Public Health published a systematic review and meta-analysis of 16 studies comprising 8,077 subjects that established a significant association between binge-watching and anxiety. In November 2022, Cyberpsychology, Behavior, and Social Networking published
3456-515: A small but positive association between social media use and anxiety, while JMIR Mental Health published a systematic review and meta-analysis of 18 studies comprising 9,269 adolescent and young adult subjects that found a moderate but statistically significant association between problematic social media use and anxiety. In May 2022, Computers in Human Behavior published a meta-analysis of 82 studies comprising 48,880 subjects that found
3600-410: A statistically significant correlation between cybervictimization and anxiety with a moderate-to-large effect size. In March 2022, JAMA Psychiatry published a systematic review and meta-analysis of 87 studies with 159,425 subjects 12 years of age or younger that found a small but statistically significant correlation between screen time and anxiety in children, while Adolescent Psychiatry published
3744-696: A systematic review and meta-analysis of 14 studies that found positive associations between problematic smartphone use and anxiety and positive associations between higher levels of problematic smartphone use and elevated risk of anxiety, while Frontiers in Psychology published a systematic review of 10 studies of adolescent or young adult subjects in China that concluded that the research reviewed mostly established an association between social networks use disorder and anxiety among Chinese adolescents and young adults. In April 2020, BMC Public Health published
3888-428: A systematic review and meta-analysis of 16 studies that established correlation coefficients of 0.31 and 0.39 between nomophobia and anxiety and nomophobia and smartphone addiction respectively. The pathophysiology of GAD is an active and ongoing area of research often involving the intersection of genetics and neurological structures. Generalized anxiety disorder has been linked to changes in functional connectivity of
4032-705: A systematic review and meta-analysis of 40 studies with 33,650 post-secondary student subjects that found a weak-to-moderate positive association between mobile phone addiction and anxiety. In November 2020, Child and Adolescent Mental Health published a systematic review of research published between January 2005 and March 2019 on associations between SNS use and anxiety symptoms in subjects between ages of 5 to 18 years that found that increased SNS screen time or frequency of SNS use and higher levels of investment (i.e. personal information added to SNS accounts) were significantly associated with higher levels of anxiety symptoms. In January 2021, Frontiers in Psychiatry published
4176-476: A systematic review of 1,747 articles on problematic social media use that found a strong bidirectional relationship between social media use and anxiety. In March 2023, the Journal of Public Health published a meta-analysis of 27 studies published after 2014 comprising 120,895 subjects that found a moderate and robust association between problematic smartphone use and anxiety. In July 2023, Healthcare published
4320-724: A systematic review of 44 studies investigating social media use and development of psychiatric disorders in childhood and adolescence that concluded that the research reviewed established a direct association between levels of anxiety, social media addiction behaviors, and nomophobia, longitudinal associations between social media use and increased anxiety, that fear of missing out and nomophobia are associated with severity of Facebook usage, and suggested that fear of missing out may trigger social media addiction and that nomophobia appears to mediate social media addiction. In March 2021, Computers in Human Behavior Reports published
4464-511: A systematic review of 52 studies published before May 2020 that found that social anxiety was associated with problematic social media use and that socially anxious persons used social media to seek social support possibly to compensate for a lack of offline social support. In June 2021, Clinical Psychology Review published a systematic review of 35 longitudinal studies published before August 2020 that found that evidence for longitudinal associations between screen time and anxiety among young people
Pregabalin - Misplaced Pages Continue
4608-463: A systematic review of 70 cross-sectional and longitudinal studies investigating moderating factors for associations for screen-based sedentary behaviors and anxiety symptoms among youth that found that while screen types was the most consistent factor, the body of evidence for anxiety symptoms was more limited than for depression symptoms. In October 2020, the Journal of Behavioral Addictions published
4752-524: A systematic review of research published from June 2010 through June 2020 studying associations between social media use and anxiety among adolescent subjects aged 13 to 18 years that established that 78.3% of studies reviewed reported positive associations between social media use and anxiety. In April 2022, researchers in the Department of Communication at Stanford University performed a meta-analysis of 226 studies comprising 275,728 subjects that found
4896-469: Is absorbed from the intestines by an active transport process mediated via the large neutral amino acid transporter 1 (LAT1, SLC7A5), a transporter for amino acids such as L -leucine and L -phenylalanine . Very few (less than 10 drugs) are known to be transported by this transporter. Unlike gabapentin , which is transported solely by the LAT1, pregabalin seems to be transported not only by
5040-627: Is a gabapentinoid medication ( GABA analogue ) which are drugs that are derivatives of γ-aminobutyric acid (GABA), an inhibitory neurotransmitter . Pregabalin acts by inhibiting certain calcium channels . When used before surgery, it reduces pain but results in greater sedation and visual disturbances. It is taken by mouth . Common side effects include headache , dizziness , sleepiness , confusion , trouble with memory, poor coordination , dry mouth , problems with vision, and weight gain . Serious side effects may include angioedema , drug misuse , and an increased suicide risk. When pregabalin
5184-420: Is a behavioral treatment based on acceptance-based models. ACT is designed with the purpose to target three therapeutic goals: (1) reduce the use of avoiding strategies intended to avoid feelings, thoughts, memories, and sensations; (2) decreasing a person's literal response to their thoughts (e.g., understanding that thinking "I'm hopeless" does not mean that the person's life is truly hopeless), and (3) increasing
5328-504: Is a short-term psychotherapy that is focused on humanistic needs of emotions when treating individuals with GAD. EFT can incorporate numerous practices such as experimental therapy, systemic therapy, and elements of CBT to allow individuals to work through difficult emotional states. The primary goal of EFT is assisting individuals in living with their vulnerable emotions and overcoming avoidance so that adaptive experiences such as compassion and protective anger can be generated in response to
5472-450: Is a summary of academic findings. Accordingly, none of the following should be taken as offering medical guidance or an opinion as to the safety or efficacy of any of the following modalities . Lifestyle factors including: stress management , stress reduction, relaxation, sleep hygiene , and caffeine and alcohol reduction can influence anxiety levels. Physical activity has shown to have a positive impact whereas low physical activity may be
5616-536: Is a type of therapy premised upon Freudian psychology in which a psychologist enables an individual explore various elements in their subconscious mind to resolve conflicts that may exist between the conscious and subconscious elements of the mind. In the context of GAD, the psychodynamic theory of anxiety suggests that the unconscious mind engages in worry as a defense mechanism to avoid feelings of anger or hostility because such feelings might cause social isolation or other negative attribution toward oneself. Accordingly,
5760-567: Is administered 2 to 3 times per day to maintain therapeutic levels. The kidney clearance of pregabalin is 73 mL/minute. Pregabalin is a GABA analogue that is a 3-substituted derivative as well as a γ-amino acid. Specifically, pregabalin is ( S )-(+)-3-isobutyl-GABA. Pregabalin also closely resembles the α-amino acids L -leucine and L -isoleucine , and this may be of greater relevance in relation to its pharmacodynamics than its structural similarity to GABA. Chemical syntheses of pregabalin have been described. Pregabalin
5904-455: Is also used. The positive effects (if any) of complementary and alternative medications (CAMs), exercise, therapeutic massage and other interventions have been studied. Estimates regarding prevalence of GAD or lifetime risk (i.e., lifetime morbid risk [LMR]) for GAD vary depending upon which criteria are used for diagnosing GAD (e.g., DSM-5 versus ICD-10 ) although estimates do not vary widely between diagnostic criteria. In general, ICD-10
Pregabalin - Misplaced Pages Continue
6048-460: Is associated with adverse neurodevelopmental outcomes (cognitive and behavioral) in children. On the other hand, evidence is conflicting for carbamazepine regarding any increased risk of congenital physical anomalies or neurodevelopmental disorders by intrauterine exposure. Similarly, children exposed lamotrigine or phenytoin in the womb do not seem to differ in their skills compared to those who were exposed to carbamazepine. There
6192-427: Is associated with weight gain, drowsiness, fatigue, dizziness, vertigo, leg swelling, disturbed vision, loss of coordination, and euphoria. It has an adverse effect profile similar to other central nervous system (CNS) depressants . Even though pregabalin is a depressant and anticonvulsant , it can sometimes paradoxically induce seizures , particularly in large overdoses . Adverse drug reactions associated with
6336-501: Is available as a generic medication in a number of countries, including the United States as of July 2019. In the United States as of July 2019 the wholesale/pharmacy cost for generic pregabalin is US$ 0.17–0.22 per 150 mg capsule. Since 2008, Pfizer has engaged in extensive direct-to-consumer advertising campaigns to promote its branded product Lyrica for fibromyalgia and diabetic nerve pain indications. In January 2016,
6480-425: Is based on asking open-ended questions and listening carefully and reflectively to patients' answers, eliciting "change talk", and talking with patients about the pros and cons of change. Some studies have shown the combination of CBT with MI to be more effective than CBT alone. Cognitive behavioral therapy (CBT) is an evidence-based type of psychotherapy that demonstrates efficacy in treating GAD and which integrates
6624-401: Is caused by an epileptic seizure. They are also often referred to as antiseizure drugs because they provide symptomatic treatment only and have not been demonstrated to alter the course of epilepsy. The usual method of achieving approval for a drug is to show it is effective when compared against placebo , or that it is more effective than an existing drug. In monotherapy (where only one drug
6768-1029: Is concern regarding pregabalin's off-label use due to the lack of strong scientific evidence for its efficacy in multiple conditions and its proven side effects. The World Federation of Biological Psychiatry recommends pregabalin as one of several first line agents for the treatment of generalized anxiety disorder, but recommends other agents such as those of selective serotonin reuptake inhibitor (SSRI) class as first line treatment for obsessive–compulsive disorder (OCD) and post-traumatic stress disorder (PTSD). For PTSD, pregabalin as complementary treatment seems to be effective. Pregabalin has anxiolytic effects similar to benzodiazepines with less risk of dependence . The effects of pregabalin appear within one week of use, and are similar in effectiveness to lorazepam , alprazolam , and venlafaxine , but pregabalin has demonstrated superiority by producing more consistent therapeutic effects for psychosomatic anxiety symptoms. Long-term trials have shown continued effectiveness without
6912-618: Is considered among all anxiety disorders (e.g., panic disorder, social anxiety disorder), genetic studies suggest that hereditary contribution to the development of anxiety disorders amounts to only approximately 30–40%, which suggests that environmental factors are likely more important to determining whether an individual may develop GAD. In regard to environmental influences in the development of GAD, it has been suggested that parenting behaviour may be an important influence since parents potentially model anxiety-related behaviours. It has also been suggested that individuals with GAD have experienced
7056-518: Is evidence for using gabapentin, lamotrigine, oxcarbazepine or topiramate as monotherapy . Lamotrigine can be included in the options for children with newly diagnosed absence seizures . The first anticonvulsant was bromide , suggested in 1857 by the British gynecologist Charles Locock who used it to treat women with "hysterical epilepsy" (probably catamenial epilepsy ). Bromides are effective against epilepsy, and also cause impotence , which
7200-427: Is frequently prescribed off-label to treat GAD. Complementary and alternative medicines (CAMs) are widely used by individuals with GAD despite having no evidence or varied evidence regarding efficacy. Efficacy trials for CAM medications often have various types of bias and low quality reporting in regard to safety. In regard to efficacy, critics point out that CAM trials sometimes predicate claims of efficacy based on
7344-479: Is generally seen as the most desirable approach to treatment. Use of medication to lower extreme anxiety levels can be important in enabling patients to engage effectively in CBT. Psychotherapeutic interventions include a plurality of therapy types that vary based upon their specific methodologies for enabling individuals to gain insight into the working of the conscious and subconscious mind and which sometimes focus on
SECTION 50
#17328012926037488-582: Is inadequate evidence to determine if newborns of women with epilepsy taking anticonvulsants have a substantially increased risk of hemorrhagic disease of the newborn . There is little evidence to suggest that anticonvulsant/ASM exposure through breastmilk has clinical effects on newborns. The Maternal Outcomes and Neurodevelopmental Effects of Antiepileptic Drugs (MONEAD) study showed that most blood concentrations in breastfed infants of mothers taking carbamazepine, oxcarbazepine, valproate, levetiracetam, and topiramate were quite low, especially in relationship to
7632-716: Is marketed as a combination drug with mecobalamin under the brand names Agemax-P, Alphamix-PG, Freenerve-P, Gaben, Macraberin-P, Mecoblend-P, Mecozen-PG, Meex-PG, Methylnuron-P, Nervolin, Nervopreg, Neurica-M, Neuroprime-PG, Neutron-OD, Nuroday-P, Nurodon-PG, Nuwin-P, Pecomin-PG, Prebel-M, Predic-GM, Pregacent-M, Pregamet, Preganerv-M, Pregeb-M OD, Pregmic, Prejunate Plus, Preneurolin Plus, Pretek-GM, Rejusite, Renerve-P, Safyvit-PR, Vitcobin-P, and Voltanerv with Methylcobalamin and ALA by Cogentrix Pharma. Anticonvulsant Anticonvulsants (also known as antiepileptic drugs , antiseizure drugs , or anti-seizure medications ( ASM )) are
7776-486: Is more inclusive than DSM-5, so estimates regarding prevalence and lifetime risk tend to be greater using ICD-10. In regard to prevalence, in a given year, about two (2%) percent of adults in the United States and Europe have been suggested to have GAD. However, the risk of developing GAD at any point in life has been estimated at 9.0%. Although it is possible to experience a single episode of GAD during one's life, most people who experience GAD experience it repeatedly over
7920-620: Is more sensitive than an amygdala in an individual without GAD or whether frontal cortex hyperactivity is responsible for changes in amygdala responsiveness to various stimuli. Recent studies have attempted to identify specific regions of the frontal cortex (e.g., dorsomedial prefrontal cortex [dmPFC]) that may be more or less reactive in individuals who have GAD or specific networks that may be differentially implicated in individuals who have GAD. Other lines of study investigate whether activation patterns vary in individuals who have GAD at different ages with respect to individuals who do not have GAD at
8064-404: Is no evidence showing that it is effective. There is no evidence and significant risk in using pregabalin for sciatica and low back pain . Evidence of benefit in alcohol withdrawal as well as withdrawal from certain other drugs is limited as of 2016. There is no evidence for its use in the prevention of migraines and gabapentin has also been found not to be useful. Exposure to pregabalin
8208-475: Is not entirely clear. During pregnancy , the metabolism of many anticonvulsants is affected. There may be an increase in the clearance and resultant decrease in the blood concentration of lamotrigine, phenytoin, and to a lesser extent carbamazepine, and possibly decreases the level of levetiracetam and the active oxcarbazepine metabolite, the monohydroxy derivative. In animal models, several anticonvulsant drugs have been demonstrated to induce neuronal apoptosis in
8352-449: Is not related to its anti-epileptic effects. Bromide also suffered from the way it affected behaviour, introducing the idea of the "epileptic personality" which was actually a result of medication. Phenobarbital was first used in 1912 for both its sedative and antiepileptic properties. By the 1930s, the development of animal models in epilepsy research led to the development of phenytoin by Tracy Putnam and H. Houston Merritt , which had
8496-671: Is not usually fatal unless mixed with another CNS depressant . Several people with kidney failure developed myoclonus while receiving pregabalin, apparently as a result of gradual accumulation of the drug. Acute overdosage may be manifested by drowsiness , tachycardia , and hypertonia . Plasma, serum, or blood concentrations of pregabalin may be measured to monitor therapy or to confirm a diagnosis of poisoning in hospitalized people. No interactions have been demonstrated in vivo . The manufacturer notes some potential pharmacological interactions with opioids , benzodiazepines , barbiturates , ethanol ( alcohol ), and other drugs that depress
8640-409: Is only approximately 30–40%, which suggests that environmental factors may be more important to determining whether an individual develops GAD. There is a strong overlapping relationship between GAD and major depressive disorder (MDD), with 72% of those with a lifelong diagnosis of GAD also being diagnosed with MDD at some point in their lives. The pathophysiology of GAD implicates several regions of
8784-680: Is premised upon the idea that anxiety is the result of maladaptive beliefs and methods of thinking. Thus, CT involves assisting individuals to identify more rational ways of thinking and to replace maladaptive thinking patterns (i.e., cognitive distortions) with healthier thinking patterns (e.g., replacing the cognitive distortion of catastrophizing with a more productive pattern of thinking). Individuals in CT learn how to identify objective evidence, test hypotheses, and ultimately identify maladaptive thinking patterns so that these patterns can be challenged and replaced. Acceptance and commitment therapy (ACT)
SECTION 60
#17328012926038928-429: Is safe. Studies have shown that higher doses of pregabalin are associated with greater efficacy. Pregabalin's use in cancer-associated neuropathic pain is controversial, though such use is common. It has been examined for the prevention of post-surgical chronic pain, but its utility for this purpose is controversial. Pregabalin is generally not regarded as efficacious in the treatment of acute pain. In trials examining
9072-453: Is selective in its binding to the α 2 δ VDCC subunit. Despite the fact that pregabalin is a GABA analogue , it does not bind to the GABA receptors , does not convert into GABA Tooltip γ-aminobutyric acid or another GABA receptor agonist in vivo , and does not directly modulate GABA transport or metabolism . However, pregabalin has been found to produce a dose-dependent increase in
9216-458: Is similar in effectiveness to lorazepam , alprazolam and venlafaxine but pregabalin has demonstrated superiority by producing more consistent therapeutic effects for psychic and somatic anxiety symptoms. Long-term trials have shown continued effectiveness without the development of tolerance and additionally, unlike benzodiazepines, it does not disrupt sleep architecture and produces less severe cognitive and psychomotor impairment. It also has
9360-471: Is strong evidence of a hereditary basis for GAD in that GAD is more likely to occur in first-degree relatives of individuals who have GAD than in non-related individuals in the same population. Twin studies also suggest that there may be a genetic linkage between GAD and major depressive disorder (MDD), which may explain the common occurrence of MDD in individuals who have GAD (e.g., comorbidity of MDD in individuals with GAD has been estimated at 60% ). When GAD
9504-418: Is taken at high doses over a long period of time, addiction may occur, but if taken at usual doses the risk is low. Use during pregnancy or breastfeeding is of unclear safety. Pregabalin was approved for medical use in the United States in 2004. It was developed as a successor to the related gabapentin . It is available as a generic medication . In 2022, it was the 91st most commonly prescribed medication in
9648-435: Is taken) it is considered unethical by most to conduct a trial with placebo on a new drug of uncertain efficacy. This is because untreated epilepsy leaves the patient at significant risk of death. Therefore, almost all new epilepsy drugs are initially approved only as adjunctive (add-on) therapies. Patients whose epilepsy is uncontrolled by their medication (i.e., it is refractory to treatment) are selected to see if supplementing
9792-469: Is unclear if it is safe for use in pregnancy with some studies showing potential harm. In December 2019, the US Food and Drug Administration (FDA) warned about serious breathing issues for those taking gabapentin or pregabalin when used with central nervous system (CNS) depressants or for those with lung problems. The FDA required new warnings about the risk of respiratory depression to be added to
9936-469: Is used as a stand-alone treatment for GAD patients. Thus, IUT focuses on helping patients in developing the ability to tolerate, cope with and accept uncertainty in their life in order to reduce anxiety. IUT is based on the psychological components of psychoeducation, awareness of worry, problem-solving training, re-evaluation of the usefulness of worry, imagining virtual exposure, recognition of uncertainty, and behavioral exposure. Studies have shown support for
10080-443: Is useful as an add-on therapy to other treatments. Its use alone is less effective than some other seizure medications. It is unclear how it compares to gabapentin for this use. The European Federation of Neurological Societies recommends pregabalin as a first line agent for the treatment of pain associated with diabetic neuropathy , post-herpetic neuralgia , and central neuropathic pain . A minority obtain substantial benefit, and
10224-749: The American Academy of Neurology and American Epilepsy Society , mainly based on a major article review in 2004, patients with newly diagnosed epilepsy who require treatment can be initiated on standard anticonvulsants such as carbamazepine , phenytoin , valproic acid / valproate semisodium , phenobarbital , or on the newer anticonvulsants gabapentin , lamotrigine , oxcarbazepine or topiramate . The choice of anticonvulsants depends on individual patient characteristics. Both newer and older drugs are generally equally effective in new onset epilepsy. The newer drugs tend to have fewer side effects. For newly diagnosed partial or mixed seizures , there
10368-577: The American Academy of Neurology and the American Epilepsy Society still recommend a number of these new drugs as initial monotherapy. In the following list, the dates in parentheses are the earliest approved use of the drug. Barbiturates are drugs that act as central nervous system (CNS) depressants , and by virtue of this they produce a wide spectrum of effects, from mild sedation to anesthesia . The following are classified as anticonvulsants: The benzodiazepines are
10512-574: The DSM-III in 1980, when anxiety neurosis was split into GAD and panic disorder . The definition in the DSM-III required uncontrollable and diffuse anxiety or worry that is excessive and unrealistic and persists for 1 month or longer. High rates in comorbidity of GAD and major depression led many commentators to suggest that GAD would be better conceptualized as an aspect of major depression instead of an independent disorder. Many critics stated that
10656-400: The International Journal of Adolescence and Youth published a systematic review of 13 studies comprising 21,231 adolescent subjects aged 13 to 18 years that found that social media screen time, both active and passive social media use, the amount of personal information uploaded, and social media addictive behaviors all correlated with anxiety. In February 2020, Psychiatry Research published
10800-476: The N-Type , and P/Q -type calcium channels. The following are gabapentinoids: Gabapentinoids are analogs of GABA, but they do not act on GABA receptors. They have analgesic, anticonvulsant, and anxiolytic effects. The following are hydantoins: The following are oxazolidinediones: The following are succinimides: The ketogenic diet and vagus nerve stimulation are alternative treatments for epilepsy without
10944-534: The amygdala and its processing of fear and anxiety. Sensory information enters the amygdala through the nuclei of the basolateral complex (consisting of lateral, basal and accessory basal nuclei). The basolateral complex processes the sensory-related fear memories and communicates information regarding threat importance to memory and sensory processing elsewhere in the brain, such as the medial prefrontal cortex and sensory cortices. Neurological structures traditionally appreciated for their roles in anxiety include
11088-557: The International Statistical Classification of Disease (ICD-10) provides a different set of diagnostic criteria for GAD than the DSM-5 criteria described above. In particular, ICD-10 allows diagnosis of GAD as follows: See ICD-10 F41.1 Note: For children different ICD-10 criteria may be applied for diagnosing GAD (see F93.80). The American Psychiatric Association introduced GAD as a diagnosis in
11232-509: The LAT1 but also by other carriers. The LAT1 is easily saturable , so the pharmacokinetics of gabapentin are dose-dependent, with diminished bioavailability and delayed peak levels at higher doses. In contrast, this is not the case for pregabalin, which shows linear pharmacokinetics and no saturation of absorption. The oral bioavailability of pregabalin is greater than or equal to 90% across and beyond its entire clinical dose range (75 to 600 mg/day). Food does not significantly influence
11376-770: The SNRIs have a higher prevalence of the side effects of insomnia, dry mouth, nausea and high blood pressure. Both SNRIs have the potential for discontinuation syndrome after abrupt cessation, which can precipitate symptoms including motor disturbances and anxiety and may require tapering. Like other serotonergic agents, SNRIs have the potential to cause serotonin syndrome, a potentially fatal systemic response to serotonergic excess that causes symptoms including agitation, restlessness, confusion, tachycardia, hypertension, mydriasis, ataxia, myoclonus, muscle rigidity, diaphoresis, diarrhea, headache, shivering, goose bumps, high fever, seizures, arrhythmia and unconsciousness. SNRIs like SSRIs carry
11520-521: The US market under the brand name Lyrica in fall of 2005. In 2017, the FDA approved pregabalin extended-release Lyrica CR for the management of neuropathic pain associated with diabetic peripheral neuropathy, and postherpetic neuralgia. However, unlike the immediate release formulation, Lyrica CR was not approved for the management of fibromyalgia or as add-on therapy for adults with partial onset seizures . In
11664-569: The United States, the FDA has approved pregabalin for adjunctive therapy for adults with partial onset seizures , management of postherpetic neuralgia and neuropathic pain associated with spinal cord injury and diabetic peripheral neuropathy , and the treatment of fibromyalgia . Pregabalin has also been approved in the European Union, the United Kingdom, and Russia for treatment of generalized anxiety disorder . Pregabalin
11808-573: The United States, with more than 7 million prescriptions. In the US, pregabalin is a Schedule V controlled substance under the Controlled Substances Act of 1970 , which means that the drug has low abuse potential compared to substances in Schedules I-IV, however, there is still a potential for misuse. Despite the low abuse potential, there have been reports of euphoria , improved happiness, excitement, calmness, and
11952-471: The amygdala, insula and orbitofrontal cortex (OFC). It is broadly postulated that changes in one or more of these neurological structures are believed to allow greater amygdala response to emotional stimuli in individuals who have GAD as compared to individuals who do not have GAD. Individuals with GAD have been suggested to have greater amygdala and medial prefrontal cortex (mPFC) activation in response to stimuli than individuals who do not have GAD. However,
12096-624: The brain expression of L-glutamic acid decarboxylase (GAD), the enzyme responsible for synthesizing GABA, and hence may have some indirect GABAergic effects by increasing GABA levels in the brain. There is currently no evidence that the effects of pregabalin are mediated by any mechanism other than inhibition of α 2 δ-containing VDCCs. In accordance, inhibition of α 2 δ-1-containing VDCCs by pregabalin appears to be responsible for its anticonvulsant , analgesic , and anxiolytic effects. The endogenous α-amino acids L -leucine and L -isoleucine , which closely resemble pregabalin and
12240-623: The brain related to GAD, or whether an individual is more or less likely to respond to a particular treatment modality. Genetic factors that may play a role in development of GAD are usually discussed in view of environmental factors (e.g., life experience or ongoing stress) that might also play a role in development of GAD. The traditional methods of investigating the possible hereditary basis of GAD include using family studies and twin studies (there are no known adoption studies of individuals who have anxiety disorders, including GAD). Meta-analysis of family and twin studies suggests that there
12384-428: The brain that mediate the processing of stimuli associated with fear, anxiety, memory, and emotion (i.e., the amygdala , insula , and the frontal cortex ). The amygdala is part of the brain that is associated with experiencing emotions. In the amygdala, the basolateral amygdala complex recognizes sensory information and activates GABAergic neurons which can cause somatic symptoms of anxiety. GABAergic neurons control
12528-410: The brain. Pregabalin has been shown to cross the placenta in rats and is present in the milk of lactating rats. In humans, the volume of distribution of an orally administered dose of pregabalin is approximately 0.56 L/kg. Pregabalin is not significantly bound to plasma proteins (<1%). Pregabalin undergoes little or no metabolism . In experiments using nuclear medicine techniques, it
12672-509: The central nervous system. ACE inhibitors may enhance the adverse/toxic effect of pregabalin. Pregabalin may enhance the fluid-retaining effect of certain anti-diabetic agents ( thiazolidinediones ). Pregabalin is a gabapentinoid medication, which are drugs that are derivatives of the γ-aminobutyric acid (GABA), an inhibitory neurotransmitter . Pregabalin inhibits certain calcium channels , namely, it blocks α 2 δ subunit -containing voltage-dependent calcium channels (VDCCs). While
12816-791: The cognitive and behavioral therapeutic approaches. The objective of CBT is to enable individuals to identify irrational thoughts that cause anxiety and to challenge dysfunctional thinking patterns by engaging in awareness techniques such as hypothesis testing and journaling. Because CBT involves the practice of worry and anxiety management, CBT includes a plurality of intervention techniques that enable individuals to explore worry, anxiety and automatic negative thinking patterns. These interventions include anxiety management training, cognitive restructuring, progressive relaxation, situational exposure and self-controlled desensitization. Several modes of delivery are effective in treating GAD, including internet-delivered CBT, or iCBT. Emotion-focused therapy (EFT)
12960-503: The company spent a record amount, $ 24.6 million for a single drug on TV ads, reaching global revenues of $ 14 billion, more than half in the United States. Up until 2009, Pfizer promoted Lyrica for other uses which had not been approved by medical regulators. For Lyrica and three other drugs, Pfizer was fined a record amount of US$ 2.3 billion by the Department of Justice, after pleading guilty to advertising and branding "with
13104-527: The concept that anxiety is learned through classical conditioning (e.g., in view of one or more negative experiences) and maintained through operant conditioning (e.g., one finds that by avoiding a feared experience that one avoids anxiety). Thus, behavioral therapy enables an individual to re-learn conditioned responses (behaviors) and to thereby challenge behaviors that have become conditioned responses to fear and anxiety, and which have previously given rise to further maladaptive behaviors. Cognitive therapy (CT)
13248-679: The course of their lives as a chronic or ongoing condition. GAD is diagnosed twice as frequently in women as in men. The diagnostic criteria for GAD as defined by the Diagnostic and Statistical Manual of Mental Disorders DSM-5 (2013), published by the American Psychiatric Association , are paraphrased as follows: No major changes to GAD have occurred since publication of the Diagnostic and Statistical Manual of Mental Disorders (2004); minor changes include wording of diagnostic criteria. The 10th revision of
13392-613: The date their marketing was approved in the US, UK and France. Data for the UK and France are incomplete. The European Medicines Agency approves drugs throughout the European Union. Some of the drugs are no longer marketed. Many of the commonly used anticonvulsant/anti-seizure medications (ASMs), such as valproate, phenytoin, carbamazepine, phenobarbitol, gabapentin have been reported to cause an increased risk of birth defects including major congenital malformations such as neural tube defects. The risk of birth defects associated with taking these medications while pregnant may be dependent on
13536-700: The developing brain. Generalized anxiety disorder Generalized anxiety disorder ( GAD ) is a mental and behavioral disorder , specifically an anxiety disorder characterized by excessive, uncontrollable and often irrational worry about events or activities. Worry often interferes with daily functioning, and individuals with GAD are often overly concerned about everyday matters such as health, finances, death, family, relationship concerns, or work difficulties. Symptoms may include excessive worry, restlessness, trouble sleeping , exhaustion, irritability, sweating, and trembling . Symptoms must be consistent and ongoing, persisting at least six months, for
13680-458: The development of tolerance , and, in addition, unlike benzodiazepines, it has a beneficial effect on sleep and sleep architecture , characterized by the enhancement of slow-wave sleep . It produces less severe cognitive and psychomotor impairment compared to benzodiazepines. A 2019 review found that pregabalin reduces symptoms, and was generally well tolerated. Although pregabalin is sometimes prescribed for people with bipolar disorder , there
13824-506: The development of epilepsy or can halt or reverse the progression of epilepsy. However, no drug has been shown in human trials to prevent epileptogenesis (the development of epilepsy in an individual at risk, such as after a head injury ). Many anticonvulsants can cause birth defects in the unborn child if taken while pregnant. Anticonvulsants are more accurately called antiepileptic drugs (AEDs) because not every epileptic seizure involves convulsion , and vice versa, not every convulsion
13968-541: The diagnosis the DSM-IV clarified was what constitutes a symptom as occurring "often". The DSM-IV also required difficulty controlling the worry to be diagnosed with GAD. The DSM-5 emphasized that excessive worrying had to occur more days than not and on a number of different topics. It has been stated that the constant changes in the diagnostic features of the disorder have made assessing epidemiological statistics such as prevalence and incidence difficult, as well as increasing
14112-458: The diagnostic features of this disorder were not well established until the DSM-III-R. Since comorbidity of GAD and other disorders decreased with time, the DSM-III-R changed the time requirement for a GAD diagnosis to 6 months or longer. The DSM-IV changed the definition of excessive worry and the number of associated psychophysiological symptoms required for a diagnosis. Another aspect of
14256-410: The difficulty for researchers in identifying the biological and psychological underpinnings of the disorder. Consequently, making specialized medications for the disorder is more difficult as well. This has led to the continuation of GAD being medicated heavily with SSRIs. The relationship between genetics and anxiety disorders is an ongoing area of research. It is broadly understood that there exists
14400-545: The distinct advantage of treating epileptic seizures with less sedation. By the 1970s, a National Institutes of Health initiative, the Anticonvulsant Screening Program, headed by J. Kiffin Penry, served as a mechanism for drawing the interest and abilities of pharmaceutical companies in the development of new anticonvulsant medications. The following table lists anticonvulsant drugs together with
14544-517: The dose and on the timing of gestation (how well developed the baby is). While trying to conceive a child and during pregnancy, medical advice should be followed to optimize the management of the person's epilepsy in order to keep the person and the unborn baby safe from epileptic seizures and also ensure that the risk of birth defects due to in utero exposure of anticonvulsants is as low as possible. Use of anticonvulsant medications should be carefully monitored during use in pregnancy. For example, since
14688-677: The efficacy of this therapy with GAD patients with continued improvements in follow-up periods. A promising innovative approach to improving recovery rates for the treatment of GAD is to combine CBT with motivational interviewing (MI). Motivational interviewing is a strategy centered on the patient that aims to increase intrinsic motivation and decrease ambivalence about change due to the treatment. MI contains four key elements: (1) express empathy, (2) heighten dissonance between behaviors that are not desired and values that are not consistent with those behaviors, (3) move with resistance rather than direct confrontation, and (4) encourage self-efficacy . It
14832-442: The emotional needs that are embedded in core emotional vulnerability. Sandplay therapy (SPT) is an intervention based on nonverbal therapeutic practices. The main objective of SPT is to allow the individual the ability to work through their emotional problems from childhood traumas (CT) through play using sand and toy figures. Although the therapy is mainly focused on nonverbal cues, verbal cues are also observed and documented during
14976-500: The exact mechanism of action of pregabalin is not definitively characterized, is believed that the main action is exhibited specifically by its binding to the α2δ subunit of VDCCs, so that this binding modulates calcium influx at the nerve terminals, thereby inhibiting the release of excitatory neurotransmitters . These excitatory neurotransmitters include glutamate , norepinephrine (noradrenaline), serotonin , dopamine , substance P , and calcitonin gene-related peptide . By inhibiting
15120-490: The exact relationship between the amygdala and the frontal cortex (e.g., prefrontal cortex or the orbitofrontal cortex [OFC]) is not fully understood because there are studies that suggest increased or decreased activity in the frontal cortex in individuals who have GAD. Consequently, because of the tenuous understanding of the frontal cortex as it relates to the amygdala in individuals who have GAD, it's an open question as to whether individuals who have GAD bear an amygdala that
15264-416: The first trimester is the most susceptible period for fetal development, planning a routine antiepileptic drug dose that is safer for the first trimester could be beneficial to prevent pregnancy complications. Valproic acid , and its derivatives such as sodium valproate and divalproex sodium , causes cognitive deficit in the child, with an increased dose causing decreased intelligence quotient and use
15408-449: The intent to defraud or mislead". Pfizer illegally promoted the drugs, with doctors "invited to consultant meetings, many in resort locations; attendees expenses were paid; they received a fee just for being there", according to prosecutor Michael Loucks. Professor Richard "Rick" Silverman of Northwestern University developed pregabalin there. The university holds a patent on it, exclusively licensed to Pfizer. That patent, along with others,
15552-578: The involvement of pharmaceuticals. The ketogenic diet consists of a high-fat, low-carbohydrate diet, and has shown good results in patients whose epilepsy has not responded to medications and who cannot receive surgery. The vagus nerve stimulator is a device that can be implanted into patients with epilepsy, especially that which originates from a specific part of the brain . However, both of these treatment options can cause severe adverse effects. Additionally, while seizure frequency typically decreases, they often do not stop entirely. According to guidelines by
15696-540: The literature regarding CAM efficacy in treating GAD. CAMs academically studied for their potential in treating GAD or GAD symptoms along with a summary of academic findings are given below. What follows is a summary of academic findings. Accordingly, none of the following should be taken as offering medical guidance or an opinion as to the safety or efficacy of any of the following CAMs. Other modalities that have been academically studied for their potential in treating GAD or symptoms of GAD are summarised below. What follows
15840-500: The lowest effective ASM dosage that will maintain their seizure control while regularly checking medication levels throughout pregnancy. Data from studies conducted on women taking antiepileptic drugs for non-epileptic reasons, including depression and bipolar disorder, show that if high doses of the drugs are taken during the first trimester of pregnancy then there is the potential of an increased risk of congenital malformations. The mechanism of how anticonvulsants cause birth defects
15984-399: The lowest risk of developing major congenital malformations compared to those exposed to other ASMs. The risk of major congenital malformations for children exposed to these ASMs were within the range for children who were not exposed to any ASMs during pregnancy. People with epilepsy can have healthy pregnancies and healthy babies. However, proper planning and care is essential to minimize
16128-461: The medication with the new drug leads to an improvement in seizure control. Any reduction in the frequency of seizures is compared against a placebo. The lack of superiority over existing treatment, combined with lacking placebo-controlled trials, means that few modern drugs have earned FDA approval as initial monotherapy. In contrast, Europe only requires equivalence to existing treatments and has approved many more. Despite their lack of FDA approval,
16272-590: The mother's level and what the fetal level would have been during pregnancy. (Note: valproic acid is NOT a recommended ASM for people with epilepsy who are considering having children.) Infant exposure to newer ASMs (cenobamate, perampanel, brivaracetam, eslicarbazepine, rufinamide, levetiracetam, topiramate, gabapentin, oxcarbazepine, lamotrigine, and vigabatrin) via breastmilk was not associated with negative neurodevelopment (such as lower IQ and autism spectrum disorder) at 36 months. Several studies that followed children exposed to ASMs during pregnancy showed that
16416-400: The nervous system by reducing feelings of stress, anxiety, and fear. When there is an inadequate number of GABAergic neurons, those negative feelings become apparent and can release somatic responses of stress. It has been suggested that individuals with GAD have greater amygdala and medial prefrontal cortex (mPFC) activity in response to stimuli than individuals who do not have GAD. However,
16560-455: The oral bioavailability of pregabalin. Pregabalin is rapidly absorbed when administered on an empty stomach, with a T max (time to peak levels ) of generally less than or equal to 1 hour at doses of 300 mg or less. However, food has been found to substantially delay the absorption of pregabalin and to significantly reduce peak levels without affecting the bioavailability of the drug; T max values for pregabalin of 0.6 hours in
16704-409: The other gabapentinoids in chemical structure , are apparent ligands of the α 2 δ VDCC subunit with similar affinity as the gabapentinoids (e.g., IC 50 =71 nM for L -isoleucine), and are present in human cerebrospinal fluid at micromolar concentrations (e.g., 12.9 μM for L -leucine, 4.8 μM for L -isoleucine). It has been theorized that they may be the endogenous ligands of
16848-424: The person's ability to keep commitments to changing their behaviors. These goals are attained by switching the person's attempt to control events to working towards changing their behavior and focusing on valued directions and goals in their lives as well as committing to behaviors that help the individual accomplish those personal goals. This psychological therapy teaches mindfulness (paying attention on purpose, in
16992-555: The prescribing information of the gabapentinoids. The FDA also required the drug manufacturers to conduct clinical trials to further evaluate their abuse potential, particularly in combination with opioids, because misuse and abuse of these products together is increasing, and co-use may increase the risk of respiratory depression. Among 49 case reports submitted to the FDA over the five-year period from 2012 to 2017, twelve people died from respiratory depression with gabapentinoids, all of whom had at least one risk factor. The FDA reviewed
17136-412: The present, and in a nonjudgmental manner) and acceptance (openness and willingness to sustain contact) skills for responding to uncontrollable events and therefore manifesting behaviors that enact personal values. Intolerance of uncertainty (IU) refers to a consistent negative reaction to uncertain and ambiguous events regardless of their likelihood of occurrence. Intolerance of uncertainty therapy (IUT)
17280-430: The rehabilitation process of the individual. SPT allows a multi-sensory experience through a safe and protected space allowing the individual the opportunity to regulate their mind and emotions. This therapeutic practice is offered in both adults and children. There is empirical evidence that exposure therapy can be an effective treatment for people with GAD, citing specifically in vivo exposure therapy (exposure through
17424-1060: The relationship between GAD and activity levels in other parts of the frontal cortex is the subject of ongoing research with some literature suggesting greater activation in specific regions for individuals who have GAD but where other research suggests decreased activation levels in individuals who have GAD as compared to individuals who do not have GAD. Treatment includes psychotherapy (e.g., cognitive behavioral therapy [CBT] or metacognitive therapy ) and pharmacological intervention. CBT and selective serotonin reuptake inhibitors (SSRI) antidepressants (e.g., escitalopram , sertraline , and fluoxetine ) are first-line psychological and pharmacological treatments; other options include serotonin–norepinephrine reuptake inhibitors (SNRI) antidepressants (e.g., duloxetine and venlafaxine ). In more severe, last resort cases, potent anxiolytics such as diazepam , clonazepam , and alprazolam are used, though not as first-line drugs as benzodiazepines are frequently abused and habit forming. In Europe, pregabalin
17568-505: The relationship between cognition and behavior. Cognitive behavioral therapy (CBT) is widely regarded as the first-line psychological therapy for treating GAD. Additionally, many of these psychological interventions may be delivered in an individual or group therapy setting. While individual and group settings are broadly both considered effective for treating GAD, individual therapy tends to promote longer-lasting engagement in therapy (i.e., lower attrition over time). Psychodynamic therapy
17712-521: The release of excitatory glutamate , whose release is considered to be elevated in epilepsy, but also that of GABA. This is probably a side effect or even the actual mechanism of action for some antiepileptic drugs, since GABA can itself, directly or indirectly, act proconvulsively. Another potential target of antiepileptic drugs is the peroxisome proliferator-activated receptor alpha . Some anticonvulsants have shown antiepileptogenic effects in animal models of epilepsy. That is, they either prevent
17856-415: The release of these neurotransmitters, pregabalin can reduce the transmission of pain signals, which helps alleviate symptoms and provides relief for patients experiencing pain, seizures, or other related symptoms. Whereas pregabalin is structurally similar to GABA, pregabalin it does not bind directly to GABA receptors, which supports the notion that its therapeutic effects are achieved through its action on
18000-432: The results of two randomized, double-blind, placebo-controlled clinical trials in healthy people, three observational studies, and several studies in animals. One trial showed that using pregabalin alone and using it with an opioid pain reliever can depress breathing function. The other trial showed gabapentin alone increased pauses in breathing during sleep. The three observational studies at one academic medical center showed
18144-646: The risk of bleeding. Overdose of an SSRI or concomitant use with another agent that causes increased levels of serotonin can result in serotonin syndrome , which can be life-threatening. First line pharmaceutical treatments for GAD also include serotonin-norepinephrine reuptake inhibitors (SNRIs). These inhibit the reuptake of serotonin and noradrenaline to increase their levels in the CNS. FDA approved SNRIs used for this purpose include duloxetine (Cymbalta) and venlafaxine (Effexor). While SNRIs have similar efficacy as SSRIs, many psychiatrists prefer to use SSRIs first in
18288-484: The risk of congenital malformations or adverse neurocognitive outcomes for the fetus while maintaining seizure control for the pregnant person with epilepsy. If possible, when planning pregnancy, people with epilepsy should switch to ASMs with the lowest teratogenic risk for major congenital malformations as well as the least risk of adverse neurodevelopmental outcomes (e.g., lower IQ or autism spectrum disorder). They should also work with their healthcare providers to identify
18432-405: The same mechanism of action , has also demonstrated effectiveness in the treatment of GAD, though unlike pregabalin, it has not been approved specifically for this indication. Nonetheless, it is likely to be of similar usefulness in the management of this condition, and by virtue of being off-patent, it has the advantage of being significantly less expensive in comparison. In accordance, gabapentin
18576-804: The same age (e.g., amygdala activation in adolescents with GAD). Traditional treatment modalities broadly fall into two categories, i.e., psychotherapeutic and pharmacological intervention. In addition to these two conventional therapeutic approaches, areas of active investigation include complementary and alternative medications (CAMs), brain stimulation, exercise, therapeutic massage and other interventions that have been proposed for further study. Treatment modalities can, and often are, utilized concurrently so that an individual may pursue psychological therapy (i.e., psychotherapy) and pharmacological therapy . Both cognitive behavioral therapy (CBT) and medications (such as SSRIs ) have been shown to be effective in reducing anxiety. A combination of both CBT and medication
18720-1414: The second patent ran out in July 2017. This cost the NHS £502 million. As of October 2017, pregabalin is marketed under many brand names: Algerika, Alivax, Alyse, Alzain, Andogablin, Aprion, Averopreg, Axual, Balifibro, Brieka, Clasica, Convugabalin, Dapapalin, Dismedox, Dolgenal, Dolica, Dragonor, Ecubalin, Epica, Epiron, Gaba-P, Gabanext, Gabarol, Gabica, Gablin, Gablovac, Gabrika, Gavin, Gialtyn, Glonervya, Helimon, Hexgabalin, Irenypathic, Kabian, Kemirica, Kineptia, Lecaent, Lingabat, Linprel, Lyribastad, Lyric, Lyrica, Lyrineur, Lyrolin, Lyzalon, Martesia, Maxgalin, Mystika, Neuragabalin, Neugaba, Neurega, Neurica, Neuristan, Neurolin, Neurovan, Neurum, Newrica, Nuramed, Paden, Pagadin, Pagamax, Painica, Pevesca, PG, Plenica, Pragiola, Prebalin, Prebanal, Prebel, Prebictal, Prebien, Prefaxil, Pregaba, Pregabalin, Pregabalina, Pregabaline, Prégabaline, Pregabalinum, Pregabateg, Pregaben, Pregabid, Pregabin, Pregacent, Pregadel, Pregagamma, Pregalex, Pregalin, Pregalodos, Pregamid, Pregan, Preganerve, Pregastar, Pregatrend, Pregavalex, Pregdin Apex, Pregeb, Pregobin, Prejunate, Prelin, Preludyo, Prelyx, Premilin, Preneurolin, Prestat, Pretor, Priga, Provelyn, Regapen, Resenz, Rewisca, Serigabtin, Symra, Vronogabic, Xablin, and Xil. It
18864-406: The severity of GAD symptoms. GAD is believed to have a hereditary or genetic basis (e.g., first-degree relatives of an individual who has GAD are themselves more likely to have GAD), but the exact nature of this relationship is not fully appreciated. Genetic studies of individuals who have anxiety disorders (including GAD) suggest that the hereditary contribution to developing anxiety disorders
19008-616: The spread of the seizure within the brain. Conventional antiepileptic drugs may block sodium channels or enhance γ-aminobutyric acid ( GABA ) function. Several antiepileptic drugs have multiple or uncertain mechanisms of action. Next to the voltage-gated sodium channels and components of the GABA system, their targets include GABA A receptors , the GABA transporter type 1 , and GABA transaminase . Additional targets include voltage-gated calcium channels , SV2A , and α2δ . By blocking sodium or calcium channels, antiepileptic drugs reduce
19152-402: The subunit and that they may competitively antagonize the effects of gabapentinoids. In accordance, while gabapentinoids like pregabalin and gabapentin have nanomolar affinities for the α 2 δ subunit, their potencies in vivo are in the low micromolar range, and competition for binding by endogenous L -amino acids has been said to likely be responsible for this discrepancy. Pregabalin
19296-518: The treatment of Generalized Anxiety Disorder. The slightly higher preference for SSRIs over SNRIs as a first choice for treatment of anxiety disorders may have been influenced by the observation of poorer tolerability of the SNRIs in comparison to SSRIs in systematic reviews of studies of depressed patients. Side effects common to both SNRIs include anxiety, restlessness, nausea, weight loss, insomnia, dizziness, drowsiness, sweating, dry mouth, sexual dysfunction and weakness. In comparison to SSRIs,
19440-692: The use of pregabalin include: Cases of recreational use, with associated adverse effects have been reported. Following abrupt or rapid discontinuation of pregabalin, some people reported symptoms suggestive of physical dependence . The FDA determined that the substance dependence profile of pregabalin, as measured by a personal physical withdrawal checklist, was quantitatively less than benzodiazepines . Even people who have discontinued short term use of pregabalin have experienced withdrawal symptoms including insomnia , headache , nausea , anxiety , diarrhea , flu-like symptoms , major depression , pain , seizures , excessive sweating , and dizziness . It
19584-488: The utility of pregabalin for the treatment of acute post-surgical pain, no effect on overall pain levels was observed, but people did require less morphine and had fewer opioid-related side effects. Several possible mechanisms for pain improvement have been discussed. Pregabalin is effective for treatment of generalized anxiety disorder . It is also effective for the short- and long-term treatment of social anxiety disorder and in reducing preoperative anxiety . However, there
19728-475: The various psychodynamic therapies attempt to explore the nature of worry as it functions in GAD in order to enable individuals to alter the subconscious practice of using worry as a defense mechanism and to thereby diminish GAD symptoms. Variations of psychotherapy include a near-term version of therapy, "short-term anxiety-provoking psychotherapy (STAPP). Behavioral therapy is therapeutic intervention premised upon
19872-499: The α2δ subunit of VDCCs. Pregabalin is a gabapentinoid and acts by inhibiting certain calcium channels . Specifically it is a ligand of the auxiliary α 2 δ subunit site of certain voltage-dependent calcium channels (VDCCs), and thereby acts as an inhibitor of α 2 δ subunit-containing VDCCs. There are two drug-binding α 2 δ subunits, α 2 δ-1 and α 2 δ-2 , and pregabalin shows similar affinity for (and hence lack of selectivity between) these two sites. Pregabalin
20016-616: Was challenged by generic manufacturers and was upheld in 2014, giving Pfizer exclusivity for Lyrica in the US until 2018. Pfizer's main patent for Lyrica, for seizure disorders, in the UK expired in 2013. In November 2018, the Supreme Court of the United Kingdom ruled that Pfizer 's second patent on the drug, for treatment of pain, was invalid because there was a lack of evidence for the conditions it covered – central and peripheral neuropathic pain. From October 2015, GPs were forced to change people from generic pregabalin to branded until
20160-606: Was effectively shaped for transportation into the brain, where it activated L-glutamic acid decarboxylase , an enzyme. Silverman hoped that the enzyme would increase production of the inhibitory neurotransmitter GABA and block convulsions. Eventually, the set of molecules were sent to Parke-Davis Pharmaceuticals for testing. The drug was approved in the European Union in 2004. The US received FDA approval for use in treating epilepsy , diabetic neuropathic pain , and postherpetic neuralgia in December 2004. Pregabalin then appeared on
20304-493: Was found to possess 6-fold higher affinity than gabapentin for α 2 δ subunit-containing VDCCs in one study. However, another study found that pregabalin and gabapentin had similar affinities for the human recombinant α 2 δ-1 subunit (K i =32 nM and 40 nM, respectively). In any case, pregabalin is 2 to 4 times more potent than gabapentin as an analgesic and, in animals, appears to be 3 to 10 times more potent than gabapentin as an anticonvulsant . Pregabalin
20448-418: Was lacking. In August 2021, a meta-analysis was presented at the 2021 International Conference on Intelligent Medicine and Health of articles published before January 2011 that found evidence for a negative impact of social media on anxiety. In January 2022, The European Journal of Psychology Applied to Legal Context published a meta-analysis of 13 cross-sectional studies comprising 7,348 subjects that found
20592-458: Was revealed that approximately 98% of the radioactivity recovered in the urine was unchanged pregabalin. The main metabolite is N-methylpregabalin . Pregabalin is generally safe in patients with liver cirrhosis . Pregabalin is eliminated by the kidneys in the urine , mainly in its unchanged form. It has a relatively short elimination half-life , with a reported value of 6.3 hours. Because of its short elimination half-life, pregabalin
20736-510: Was synthesized in 1990 as an anticonvulsant . It was invented by medicinal chemist Richard Bruce Silverman at Northwestern University in Evanston, Illinois . Silverman is best known for identifying the drug pregabalin as a possible treatment for epileptic seizures . During 1988 to 1990, Ryszard Andruszkiewicz, a visiting research fellow, synthesized a series of molecules requested by Silverman. One looked particularly promising. The molecule
#602397