Generalized Anxiety Disorder Psychobiology and Neuroscience

GENERALIZED ANXIETY DISORDER

Psychobiology and Neuroscience: Generalized Anxiety Disorder

Introduction

From the onset, it would be prudent to note that from time to time, most people feel anxious about diverse events or occurrences in life. This is normal. However, it should be noted that when the said anxiety is persistent, exaggerated and/or excessive, then a person could be likely suffering from Generalized Anxiety Disorder (GAD). In the past, various interventions have been formulated in an attempt to treat this particular condition. The main treatment approaches on this front happen to be medications and psychotherapy. This text concerns itself with the medications approved in the treatment of GAD. In so doing, the main focus will in this case be neurobiology and drug mechanisms of action.

Discussion

In essence, there are various medications that have proven effective and have thus been approved for the treatment of GAD. These medications are especially instrumental in efforts to ease symptoms of the condition. The medications that will be taken into consideration in the subsequent sections of this text are:

a) Antidepressants

b) Benzodiazepines

Antidepressants

These, as Gerlach and Gloster (2020) point out, are essentially considered first-line medications in the treatment of GAD. This is to say that they are routinely used as the first choice of medications for patients diagnosed with GAD. Unlike benzodiazepines, which are usually used in the short-term treatment of the condition, antidepressants come in handy in the longer-term treatment of GAD. In this case, there would be need to take into consideration the mechanism of action of antidepressants in the selective serotonin reuptake inhibitor (SSRI) as well as the selective serotonin-norepinephrine reuptake inhibitor (SNRI) class.

i. Selective Serotonin Reuptake Inhibitors

To begin with, when it comes to SSRI’s Gerlach and Gloster (2020) are categorical that “as the name suggests, SSRIs exert action by inhibiting the reuptake of serotonin, thereby increasing serotonin activity” (213). It therefore follows that SSRIs’ therapeutic effect is largely founded upon their ability to bring about an increase in deficient serotonin. However, as Strawn, Geracioti, Tajdev, Clemenza, and Levine (2019) indicate, in some instances, SSRIs faintly inhibit the reuptake mechanisms for dopamine and norepinephrine. Essentially, as a neurotransmitter, serotonin happens to be instrumental in the relay or transmission of messages between neurons. Thus, more serotonin (specifically at the postsynaptic membrane in the synapse) effectively means better transmission of the said messages. Examples of SSRIs are fluoxetine, sertraline, paroxetine, as well as citalopram. These will be briefly taken into consideration below.

With regard to fluoxetine, Strawn, Geracioti, Tajdev, Clemenza, and Levine (2019) are categorical that this happens to be one of the SSRIs that were first introduced in the country in the 1970s. According to the authors, the therapeutic effect of this particular SSRI is largely rooted in its ability to bring about an increase in serotonergic transmission. However, the authors also indicate that the drug has been shown to have dopaminergic as well as noradrenergic effects. According to Gerlach and Gloster (2020), the drug is well tolerated among both pediatric and adult patients diagnosed with GAD.

Next, sertraline has also proven to be effective in the treatment of GAD. For instance, in a study seeking to evaluate the effectiveness of this particular drug among pediatric patients presenting with symptoms consistent with GAD, it was found that in comparison to a placebo, it brought about significant improvements in as far as reduction of symptoms is concerned (Strawn, Geracioti, Tajdev, Clemenza, and Levine, 2019). The authors further indicate that among adults, the therapeutic effect of sertraline is further enhanced following the incorporation of CBT.

Paroxetine, in the words of Strawn, Geracioti, Tajdev, Clemenza, and Levine (2019), “potently inhibits 5-HT reuptake and also blocks some reuptake of norepinephrine” (1060). The authors further indicate that research studies conducted in the past have indicated that this particular drug is effective in the treatment of GAD among adult patients.

Lastly, in as far as the SSRIs identified in this discussion are concerned, citalopram happens to be one of the most recent SSRIs introduced in the country. Gerlach and Gloster (2020) point out that in comparison to other SSRIs, the drug happens to be rather selective in as far as the transportation of serotonin is concerned. It should also be noted that citalopram, unlike other drugs in this particular category, doesn’t experience or go through first-pass metabolism (Geracioti, Tajdev, Clemenza, and Levine, 2019).

ii. Selective Serotonin-Norepinephrine Reuptake Inhibitors

Both serotonin and norepinephrine are instrumental when it comes to the regulation of various emotions as well as functions. In essence, whereas norepinephrine is largely linked to the fight or flight response and plays a significant role in a person’s response to anxiety (as well as stress), serotonin has been closely associated with mood (as well as sleep). According to Durbano (2013), in basic terms, SNRIs prevent the rapid absorption of both serotonin and norepinephrine. More specifically, in the words of the author, “they block the reuptake of serotonin (5HT) and noradrenaline (NA) (norepinephrine) by inhibiting the serotonin and noradrenaline transporters” (119). Thus, it should be noted that SNRIs could be distinguished from SSRIs, which have been discussed above, in the sense that the latter increase serotonin only. Two examples of SNRIs which will be briefly discussed below are; venlafaxine and duloxetine.

Venlafaxine, as Strawn, Geracioti, Tajdev, Clemenza, and Levine (2019) observe has been approved by the Federal Drug Administration (FDA) for the treatment of a number of conditions including; social anxiety disorder (SAD), panic disorder, major depressive disorder (MDD), and generalized anxiety disorder (GAD). According to the authors, the drug derives its therapeutic effect from its inhibition of serotonin and norepinephrine reuptake transporters via o-desmethylvenlafaxine which happens to be its active metabolite. The authors further indicate that past studies have indicated that this particular drug happens to be rather effective in the reduction of GAD symptoms among adults. Efficacy among pediatric patients, specifically those between the ages of 7 and 17, has also been suggested by some studies (Strawn, Geracioti, Tajdev, Clemenza, and Levine, 2019).

On the other hand, when it comes to duloxetine, Durbano (2013) points out that the said drug has been approved by the FDA for the treatment of GAD and several other conditions including, but not limited to; chronic musculoskeletal pain, fibromyalgia, diabetic peripheral neuropathic pain, and major depressive disorder (MDD). Various studies conducted in the past, as Strawn, Geracioti, Tajdev, Clemenza, and Levine (2019) indicate have indicated that among pediatric patients and adults, the drug does result in the alleviation of symptoms of anxiety and bring about or inform better outcomes on the functional front. It should also be noted that as the authors in this case further point out, this happens to be the only antidepressant with a seal of approval from the FDA for the treatment of generalized anxiety disorder among adolescents and children.

Benzodiazepines

In essence, these belong to a classification of central nervous system depressants that come in handy in efforts to minimize the intensity of GAD psychological symptoms. Benzodiazepines, according to Marker and Aylward (2011), “act by facilitating the binding of the inhibitory neurotransmitter GABA at various GABA receptors throughout the CNS” (297). This is an assertion further advanced by Strawn, Geracioti, Tajdev, Clemenza, and Levine (2019) who indicate that these medications potentiate endogenous GABA effects by functioning as allosteric modulators as well as via their action of binding to the GABAA receptor. The authors further indicate that benzodiazepines were widely utilized in the treatment of GAD before SNRIs and SSRIs were introduced and gained mainstream utilization in as far as generalized anxiety disorder pharmacotherapy is concerned. One key difference between benzodiazepines and the antidepressant medications highlighted elsewhere in this text is that the emergence of the therapeutic effects of the former happens to be soon after administration.