Question

In your opinion, does this combination of medications make clinical sense?

Yes

No

Attending physician’s mental notes: initial evaluation

This patient has chronic GAD without many comorbidities

His GAD exacerbations are often triggered by social stressors

He is motivated, bright, and compliant

His medication regimen is interesting, and even though it was provided by three different clinicians, it makes rational sense

• – First, the paroxetine-CR was causing side effects at higher doses, thus augmenting with other agents while keeping paroxetine-CR at a low therapeutic dose makes clinical sense

• – Second, hydroxyzine (Vistaril/Atarax) was being used as an anti-allergy medication, but it is approved as an antihistaminergic anxiolytic

• – Third, tiagabine (Gabitril) is an anti-epilepsy medication that has failed monotherapy trials in GAD and PTSD, but has some supportive data as an augmentation strategy for TRA when combined with SSRIs

  • It is a GAT1 GABA reuptake inhibitor that functions to increase endogenous synaptic GABA levels

  • Idiosyncratically, this may cause seizures in non-epileptics who are prescribed this medication in off-label situations

• – Fourth, this regimen facilitates serotonin by blocking the SERT, or reuptake pump, antagonizes histamine activity at the H1 receptor, and facilitates GABA by blocking GAT1 transporters

  • All of these mechanisms are complementary, do not overlap in pharmacodynamic redundancy, and look to manipulate neural pathways involved in the etiology of anxiety

Question

Which of the following would be your next step?

Increase the paroxetine (Paxil-CR)

Increase the tiagabine (Gabitril)

Increase the hydroxyzine (Vistaril)

Augment the current medications with a fourth agent such as an NRI, a 5-HT1A receptor partial agonist, or a BZ anxiolytic

Consider him a partial responder on this regimen, which is unacceptable, and streamline and convert him to a less complicated regimen with an SNRI, TCA, or MAOI monotherapy

Attending physician’s mental notes: initial evaluation (continued)

The combination the patient presents with is a good one, covering many mechanisms of action that are individual, yet complementary

There is a significant family history of addiction, so avoiding BZs makes sense

He has room to increase any one of his three current medications, but this will likely exacerbate his sexual and fatigue-based side effects further, which the patient will not appreciate

Further investigation

Is there anything else you would especially like to know about this patient?

What about details concerning his past trauma history?

• – Grew up in less than ideal circumstances with an alcoholic and verbally abusive father

• – Denies overt reliving symptoms but clearly has hyperarousal (worry, muscle tension) thought currently to be from GAD

• – Denies avoidant or phobic behavior

• – Feels psychotherapy has been very helpful

What about details regarding personality style and coping skills?

• – The patient is socially engaging, hard working, and very active

• – If he is not working, he is exercising and being active

• – Never seems to sit still as he has always been a busy person

• – Keeping busy and exercising allows him to remain calm and more focused

• – Feels he would be distracted and less attentive if he did not have time to exercise