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Can Anticonvulsants Help Patients With Anxiety Disorders?


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#1 Forum Admin

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Posted 23 June 2011 - 07:52 PM

Can Anticonvulsants Help Patients With Anxiety Disorders?
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  • Published 06/17/2011
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../templates/DFDefault/Images/DFImages/mkquote_balloon_l.gif By Forum Admin ../templates/DFDefault/Images/DFImages/mkquote_balloon_r.gif ../templates/DFDefault/Images/DFImages/mkquote_top_r.gif [size="2"][i]
Psychiatric Times. Vol. 26 No. 2


Can Anticonvulsants Help Patients With Anxiety Disorders?

What Does the Evidence Show?
../content_images/Anticonvulsants2.jpg

By Marco Mula, MD, PhD | February 1, 2009
Dr Mula is research associate and consultant in neurology and neuropsychiatry in the department of clinical and experimental medicine, section of neurology, The Neuro­psy­chi­atry Research Group at the Amedeo Avogadro University in Novara, Italy. Although he received no financial support for the prepa­ration of this article, Dr Mula reports that through the years he has received travel support and speakers fees from various pharmaceutical companies who are involved in the manufacture of antiepilectic drugs, in­cluding Novartis, Pfizer, UCB-Pharma, Janssen-Cilag, and Sanofi-Aventis.
<br style="font-weight: bold;">
In This Special Report:

  • The Intricacies of Diagnosis and Treatment, by Thomas L. Schwartz, MD
  • Strategies for Assessing and Treating Comorbid Panic and Generalized Anxiety Disorder, by Kristalyn Salters-Pedneault, PhD
  • Can Anticonvulsants Help Patients With Anxiety Disorders? by Marco Mula, MD, PhD
  • SSRIs as Antihypertensives in Patients With Autonomic Panic Disorder, by Sean Hood, MBBS, MSc
Achieving Remission in Generalized Anxiety Disorder, by Laura A. Mandos, PharmD, Jennifer A. Reinhold, PharmD, and Karl Rickels, MD


Anxiety Disorders
Anxiety disorders are chronic conditions that follow a relapsing/remitting course.1 The evidence to support this view comes primarily from cross-sectional and retrospective assessments of duration of illness and, in part, from prospective studies. The waxing and waning nature of panic disorder and generalized anxiety disorder (GAD), for example, has been clearly demonstrated. Much less information is available about the course of illness of social phobia. However, both community studies and patient samples suggest an age of onset of social phobia in mid to late teens with a chronicity that is equal to or greater than that of panic disorder.2 Nevertheless, this recognition has not reshaped our basic treatment approach, which focuses almost entirely on the acute control of symptoms and only secondarily acknowledges relapse prevention.

In addition, the natural history of anxiety disorders is frequently complicated by Axis I and Axis II comorbidity that seems to be significantly higher among patients who seek treatment than in persons in the community who are not in treatment.1 In fact, it has been estimated that 73% of patients with panic disorder had other comorbid conditions that ranged from major depression to substance abuse until the onset of the Axis II disorders, mostly cluster C type 1 to 2. It is, therefore, evident that any long-term anxiolytic treatment strategy must take account of these high rates of comorbidity that appear to develop during the longitudinal phase of the anxiety disorder.

A variety of drug classes have been shown to be effective in treating anxiety disorders. SSRIs are the current gold standard for anxiety disorders. Effective in about 50% to 60% of patients, serotonin noradrenalin reuptake inhibitors are now considered the gold standard specifically for panic disorder and GAD. Benzodiazepines have a rapid onset of action, but their long-term use may lead to complications, such as abuse liability, dependence, and withdrawal risk if the dosage is not tapered properly. Moreover, in some patients, benzodiazepines may cause sedative effects and cognitive deficits that significantly affect quality of life and social functioning.

The basis for the use of anticonvulsant drugs in treating anxiety disorders can be found in the main cerebral structures involved in fear circuits. Although numerous brain regions are likely to be involved, the amygdala and the hippocampus play a key role.3 The amygdala is im­portant in experiencing fear and its autonomic and endocrine response through the output to the hypothalamus, while the output to periaqueductal gray matter is mainly implicated in avoidance behavior, which is also typical of fear response.4 In addition, the hippocampus is important in the re-experiencing of fear and the cognitive aspects of fear and anxiety.

The reduction of an excessive output from these neurons may theoretically diminish anxiety symptoms. In fact, anticonvulsant drugs exert their antiseizure activity by decreasing the excessive outbursts from epileptic neurons. Therefore, these drugs could reduce symptoms of anxiety by decreasing neuronal activation within fear circuits. Unlike other drug classes, anticonvulsants are not usually categorized according to their mechanisms of action or chemical structure. This is because their actions are not completely understood at the molecular level, and current knowledge indicates that almost all antiepileptic drugs have more than one mechanism of action (Table 1). Among all known mechanisms, the potentiation of g-aminobutyric acid (GABA)-ergic inhibition and the modulation of voltage-activated calcium channels may be most responsible for the pathophysiology of anxiety.4
<br style="font-weight: bold;">GABAA receptors
GABA is the principal inhibitory neurotransmitter and, along with serotonin and noradrenalin, is one of several neurotransmitters that appear to be involved in the pathogenesis of anxiety.3 Drugs that stimulate GABAA receptors, such as benzodiazepines, have both anxiolytic and antiseizure effects via GABAA mediated reduction of neuronal excitability. The GABAA receptor subtype regulates excitability and rapid changes in fear arousal, such as anxiety, panic, and acute stress response.

However, the sedative hypnotic effect of benzodiazepines is the result of an allosteric-positive modulation of GABAA receptors that contain the alpha-1 subunit. The anxiolytic effect seems to be related to an allosteric modulation of receptors that contain the alpha-2 subunit.5 It is evident that GABA modulation is a determinant for both anxiety and seizures: in fact, GABAA antagonists produce convulsions in animals. A study using pos­itron emission tomography showed that patients with panic disorder have a decrease in GABAA receptor binding.6

Not all classic GABA-ergic anticonvulsants exert helpful psycho­active properties. Although their pharmacological profile suggests anxio­lytic properties, barbiturates, vigabatrin(Drug information on vigabatrin), and topiramate(Drug information on topiramate) may have treatment-emergent psychiatric adverse effects. Agitation and hyperactivity have been described with barbiturates, especially in children, and it is well documented in the neurological literature that both vigabatrin and topiramate are associated with depression and psychoses.7 This may be a consequence of GABA-ergic neurotransmission. The emerging understanding of different roles for phasic or synaptic inhibition and tonic inhibition mediated by different subpopulations of GABAA receptors may lead to targeted compounds for anxiety disorders.

Calcium channel blockers
Calcium channel blockers represent another class of molecules that can be of relevance in anxiety. They have been shown to be of value in ameliorating symptoms in animal models of anxiety.8 In general terms, calcium channels can be categorized according to their biophysical and pharmacological properties in 2 main subfamilies: high-voltage

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#2 Guest_chapstyck1979_*

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Posted 23 July 2011 - 03:58 AM

My (lay person) rhetorical thoughts and questions concerning scientific approaches to psychiatric illness treatments derived from this article:
Since stumbling upon information regarding taking GABA supplements (gamma amino butyric acid), which is a "naturally occurring amino acid in the brain functioning as a neurotransmitter that helps ease your mind during stressful situations" among other things... I have been VERY interested in this topic and this is a great article but I have so many questions! I have selected passages that add to my questioning.....


"The amygdala is important in experiencing fear and its autonomic and endocrine response through the output to the hypothalamus, while the output to periaqueductal gray matter is mainly implicated in avoidance behavior, which is also typical of fear response.In addition, the hippocampus is important in the re-experiencing of fear and the cognitive aspects of fear and anxiety...

The reduction of an excessive output from these neurons may theoretically diminish anxiety symptoms. In fact, anticonvulsant drugs exert their antiseizure activity by decreasing the excessive outbursts from epileptic neurons. Therefore, these drugs could reduce symptoms of anxiety by decreasing neuronal activation within fear circuits...
Among all known mechanisms, the potentiation of g-aminobutyric acid (GABA)-ergic inhibition and the modulation of voltage-activated calcium channels may be most responsible for the pathophysiology of anxiety.


Meaning... The mechanisms that CAUSE the amino acid "gamma-aminobutyric acid" (GABA) to be blocked or inhibited are most likely the reason for anxiety...


GABA is the principal inhibitory neurotransmitter and, along with serotonin and noradrenalin, is one of several neurotransmitters that appear to be involved in the pathogenesis of anxiety. Drugs that stimulate GABAA receptors, such as benzodiazepines, have both anxiolytic and antiseizure effects via GABAA mediated reduction of neuronal excitability. The GABAA receptor subtype regulates excitability and rapid changes in fear arousal, such as anxiety, panic, and acute stress response."


So... GABA REDUCES the fear/anxiety basically produced and perceived by the amygdala/hypothalamus/hippocampus and the anticonvulsant drugs REGULATES the GABA RECEPTORS...


"It is evident that GABA modulation is a determinant for both anxiety and seizures: in fact, GABAA antagonists produce convulsions in animals. A study using positron emission tomography showed that
patients with panic disorder have a decrease in GABAA receptor binding."


Where the anxiety occurs because GABA receptors are not binding properly with the GABA enzymes...

But...

"Not all classic GABA-ergic anticonvulsants exert helpful psychoactive properties... This may be a consequence of GABA-ergic neurotransmission. The emerging understanding of different roles for phasic or synaptic inhibition and tonic inhibition mediated by different subpopulations of GABAA receptors may lead to targeted compounds for anxiety disorders..."


etc etc etc. My biggest question is, would persons with anxiety disorders taking an anticonvulsant benefit by taking GABA supplements as a natural AID to the GABA receptors? Or.. has this not been proven to be effective? Could it hurt to try? Basically, I'm tired of unecessary fears overtaking my social outlook on life.


ps. You're amazing and I appreciate your research!

Edited by chapstyck1979, 23 July 2011 - 04:04 AM.


#3 REG

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Posted 06 October 2012 - 12:50 PM

Really interesting article and interesting response - more than a year ago! I've been interested in trying pregabalin but so far my doc hasn't let me. Mirtazipine didn't work and just made me hungry all the time :-/ Venlafaxine works but I seem to be developing a tolerance/ needing higher doses. Diazepam 5mg doesn't work for me but Tamazepan did, but it's so addictive they don't usually prescribe it in the Uk any more. Alcohol works a treat, but has it's own problems...

Has anyone here tried pregabalin for GAD? I'd be very interested to hear.

#4 REG

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Posted 07 October 2012 - 07:54 AM

To be clear I am NOT recommending alcohol to treat GAD - beneficial effects far too short-acting and harmful effects much too numerous!




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