Combination SSRIs/TCAs: Your guide to treating behavioral disorders

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Mar 01, 2007

Some of the newer medications (e.g., Effexor; venlafaxine) have the beneficial effects of TCAs and SSRIs combined, minimizing side effects.

This means they will stimulate both the more specific and less specific neurochemical receptors, and will affect both norepinephrine and serotonin, but at different rates than would the SSRI or TCA alone. As a result, some of these medications can have greater treatment effects for some patients. All of them still have their patents at this writing; that can make them a little pricier than some of the other older medications.

In vivo combination treatment

BZs can be used in combination with TCAs and SSRIs when called for. For example, many dogs with separation anxiety are also afraid of storms. Storms do not happen every day in most parts of the country, so giving a daily medication is unnecessary. The dog can take a TCA like clomipramine every day, and the BZ alprazolam as needed. This means that for 20 days a month the dog may get the TCA twice a day, but for 10 days it also gets the alprazolam as needed if there is a 50 percent chance or greater of storms.

Because dogs use up alprazolam quickly and have few sedative effects of repeat dosing if the dose chosen is correct, the dog may get alprazolam three or four times a day during those 10 days of storms.

If the dog lives in an area where there is a true storm season, the decision to give the dog a daily BZ plus a daily TCA might be justified. For example, alprazolam could be given twice a day during the season, and more often as needed. This raises the threshold for reactivity, and lets the dog take advantage of the pharmacokinetics of the medication by constantly boosting both parent compound and intermediate metabolites, some of which can be biologically helpful.

BZs can become the victim of physiological tolerance, meaning that the animal will need more with time, but at the levels used for routine treatment this happens less often than one might expect. If an increase in medication is required to sustain a good clinical effect, this is not a problem as long as:

  • The vet is sure that it is the dog or cat who is actually getting the drugs.
  • A serum biochemistry profile indicates that the patient's metabolic capabilities are not impaired by the medication(s).

In fact, this is exactly why pre-medication laboratory evaluation is needed: How will you know if your treatment is having an adverse effect if you do not have a baseline against which to compare later blood work?

So, unless my clients have to choose between buying the drug and paying for lab work, or, by obtaining blood I might make the patient behaviorally worse, I want recent lab work on all my patients.

To use BZs, TCAs and SSRIs effectively, we need to acknowledge that we actually don't know very much about the disposition of these medications in our patients, and that we lack knowledge of their effects of the cytochrome system — specifically the CPY 450 system — on metabolism of these medications.

That said, dogs appear to be much like humans: there are ultra-fast metabolizers, who will need more medication than average, ultra-slow metabolizers, who will need less, and those who are normal, fast metabolizers, for whom the target dose is just fine.

To establish these ranges in dogs and/or cats, we would need to treat a large number of patients with the same drug for the same condition, involving the same inclusion and exclusion criteria, then obtain genetic samples and intermediate metabolite samples from the patients studied. This is a project that needs to be done, and in which I have great interest. If anyone has ideas about how it could be done, they should let me know.

Only by making good clinical observations about the behavioral patterns and their changes during treatment can veterinarians use this type of knowledge to benefit their patients.

There is no ideal drug to control or treat both of the chronic and sporadic types of anxieties. The best way is to use the two different drugs in a rational way. This means that you need to understand how they interact for effect and for side effects.