Do SSRIs Affect GABA Levels For Anxiety?

Hello I’m Dr. Carlo with AnxietyBoss.com, and I’m here to answer your questions about anxiety. A viewer asked the following question: do SSRIs affect GABA levels for anxiety?

Okay, so I’ll answer this question. GABA is a neurotransmitter in the brain which is important for the development and the treatment of anxiety. GABA is a neurotransmitter in the central nervous system, and it is an inhibitory neurotransmitter- so things like benzodiazepines such as Ativan (lorazepam) or Klonopin (clonazepam) affect GABA levels, in that they increase GABA in the brain, and this increase in GABA thereby leads to decreased anxiety symptoms. However, the viewer asked me if SSRIs such as Zoloft and Prozac, do these SSRIs also affect GABA levels, because he heard that somehow through a negative feedback loop that it may somehow affect GABA levels.

The answer is: no.

SSRIs do not affect GABA levels, but let me give you the neurobiology of anxiety, how anxiety develops, and how treatments such as SSRIs, benzodiazepines, and psychotherapy (such as cognitive behavioral therapy) affect the brain and thereby lead to decreased anxiety symptoms. So when you look at the development of anxiety, what happens is that there is a malfunction in the amygdala. So the fear circuits of the brain are centred on a part of the brain called the amygdala. When you have anxiety, these fear circuits based on the amygdala are overactive. So they are hyperactive and malfunctioning, and thereby causes anxiety symptoms.

So when you are trying to decrease anxiety what you’re trying to do when you’re treating anxiety is to decrease the hyperactivity of the fear circuits based on the amygdala. So in the brain, the fear circuits are modified by different neurons. Again, when you have anxiety, the amygdala is hyperactive. The amygdala in turn is innervated by serotonin neurons, and it’s also innervated by GABA neurons. So when you have an increase of the serotonin signal from the serotonin neuron to the amygdala, what happens is this increase in the serotonin signal from the serotonin neurons then leads to a suppression of the amygdala, and thereby it quells the hyperactivity of the amygdala, and thereby decreases anxiety symptoms. That explains why medications like SSRIs can treat anxiety, as SSRIs increase the signal of the serotonin neurons, and this increase in the serotonin neuron signal to the amygdala suppresses it, and leads to a decrease in anxiety symptoms.

You can also decrease anxiety and suppress the amygdala by the GABA neurons which also innervate the amygdala independently. So these GABA neurons are affected by medications such as benzodiazepines. Benzodiazepines increase the GABA signal. In addition, curiously and interestingly, psychotherapy such as cognitive behavioral therapy (CBT) also increases the GABA signal. So what happens when you increase the GABA signal via benzodiazepines or via psychotherapy is that they also suppress the amygdala and thereby leads to a decrease in anxiety symptoms.

So if you have severe anxiety symptoms, such as severe panic disorder with severe panic attacks for instance, we know clinically what works best is a multi-modal treatment approach. Instead of just focusing on one treatment modality, the best clinical practice to date that is supported by research studies is that the multimodal treatment approach is most effective. When you go back to the neurobiology of anxiety, as I told you before, the amygdala is innervated by both serotonin neurons and GABA neurons. With severe anxiety symptoms, you want all of these modifiers that deal with all of these pathways that lead to a decrease in anxiety symptoms. You want all these pathways to be working, so if you have severe anxiety symptoms, you want to have an increase in the serotonin signal and you also want to have an increase in the GABA signal. You can accomplish this with a multi-modal approach- serotonin neurons get activated by SSRIs and GABA neurons get activated by benzodiazepines and psychotherapy (CBT). So when you have both the serotonin neurons and the GABA neurons activated concurrently, then both of these pathways leads to a decrease in the hyperactivity of the amygdala, and thereby leads to a decrease in anxiety symptoms.

So if you have severe anxiety symptoms such as panic attacks, obsessive compulsive disorder (OCD) or post-traumatic stress disorder (PTSD) symptoms, then you want a multimodal treatment approach which focuses on modifying and increasing the signals of both the serotonin neurons and the GABA neurons. This is accomplished via treatments with SSRIs for the serotonin neurons and benzodiazepines and CBT for the GABA neurons.

I hope this answers your question. I’m Dr. Carlo…thank you for visiting.

photo credit: National Institutes of Health (NIH) Illustration of neurotransmitter via photopin (license)