Attending physician’s mental notes: interim follow-up visits through five years

Patient has received a fair amount of anxiety stabilizing treatment from his current two medications (SSRI plus SGRI) for many years

While there are certainly adjustment disorder issues here, he does genuinely have increased GAD symptoms

His therapist provides PDP, thus giving him a course of CBT for his performance anxiety is unlikely to help now, as disturbing transference issues should be avoided

As he is comfortable on his current medications, adding a third agent to re-establish his remission makes sense

Case outcome: interim follow-up visits through six years

The patient considers much of his newer stress and dysphoria to arise from performance anxiety in his new work

Starts propranolol (Inderal) up to 30 mg/d as needed, to use specifically for performance anxiety symptoms, and he does well

For the baseline GAD symptoms, he continues on tiagabine (Gabitril) and paroxetine-CR (Paxil-CR) but is augmented next with L-methylfolate (Deplin) 7.5 mg/d

• – Ideally this can boost the anxiolytic effects of his SSRI and help avoid the need to increase the SSRI further, thus avoiding sexual side effects

Note: L-methylfolate (Deplin) is an approved medical food that may boost the effectiveness of antidepressants in treating depression. Why might this work in anxiety disorders?

SSRIs treat both depression and anxiety, so should L-methylfolate (Deplin) augmentation

L-methylfolate theoretically enhances the one-carbon metabolic cycle, which lends to the ability of neurons to make more monoamines, such as serotonin

L-methylfolate’s ability to escalate serotonin levels allows SSRIs to be more effective in that SERT inhibition now accounts for more synaptic serotonin availability when compared to those levels prior to augmentation

• – Essentially, the SSRI now has more serotonin to work with

• – This mechanism theoretically should enhance serotonin antidepressant or anxiolytic efficacy in TRD or TRA

The patient does not respond to the L-methylfolate (Deplin) augmentation and it is discontinued

Switches to a combination strategy where the 5-HT1A partial receptor agonist-approved GAD anxiolytic, buspirone (BuSpar) 30 mg/d, is added to the SSRI paroxetine-CR (Paxil-CR) while the SGRI tiagabine (Gabitril) is tapered off and deemed to be ineffective at this point

• – Around this time, warnings that tiagabine may induce seizures in certain non-epilepsy patients also led to the decision to not escalate it further and to discontinue its use

The combination of buspirone/paroxetine-CR failed to obtain remission

Question

What would you do next?

Insist he change to a CBT therapist

Augment with an alpha-2-delta calcium channel blocking antiepileptic medication such as gabapentin (Neurontin) or pregabalin (Lyrica)

Deem that his SSRI is also ineffective and switch to an SNRI

Deem that his SSRI is also ineffective and switch to a BZ

Attending physician’s mental notes: interim visits through year six

This patient is appearing to have more significant TRA now

He is being treated by a competent psychotherapist and is compliant with his medications

He is very agitated at times, which is interfering with his work

Would like to use an as-needed BZ while we work out a longer-term strategy, but worries about addiction given his family history

Failed an SSRI, a 5-HT1A receptor partial agonist, an antihistamine anxiolytic, and an SGRI