Performance in practice: confessions of a psychopharmacologist

What could have been done better here?

• – Psychopharmacologists do not act in a vacuum

  • This patient’s rheumatologist began the patient on two medications, which generally are warranted in the treatment of certain FM patients (approved pregabalin and off-label modafinil)

  • Outside treating her FM, these medications may actually have helped to dampen her anxiety, improve her cognition, and even depression

  • However, the use of these multiple medications ended with side-effect issues and delayed the psychiatrist’s more aggressive monotherapy approach

  • Earlier discussion with the outside provider may have avoided this intervention

• – Inpatient providers should have been aware that her SNRI and her BZ would likely produce withdrawal syndromes when abruptly stopped

  • A parenteral BZ should have been started earlier

  • There is no easy way to provide parenteral antidepressants outside possible use of intravenous clomipramine

  • Certain opiate pain medications (tramadol, meperidine, fentanyl) possess SRI and NRI properties, and could be utilized for acute pain management and might avoid SNRI discontinuation syndrome

    • Recollect that this patient was taking fentanyl throughout her care in this case

Possible action items for improvement in practice

• – Research guidelines and review articles regarding treating FM

  • Many rational polypharmacy approaches and techniques that are employed in the treatment of MDD may be applied similarly to treating FM

  • The SNRI class has two approvals (duloxetine and milnacipran) that may be able to help comorbid FM patients

• – Understand the complexity of drug delivery systems

  • Many psychotropics now come in immediate-, intermediate-, and slow-release preparations

  • Some agents are produced as prodrugs and as patches

  • Some drugs require to be taken with food, others without for optimal dosing and absorption

  • Understanding the mechanism of release, rate of absorption, and pharmacokinetics may mean the difference between having efficacy or not, side effects or not

Tips and pearls

Generally, the slower the release mechanism or process that a drug preparation utilizes, the fewer side effects it will have

• – Lower initial blood plasma levels will be maintained and avoidance of initial rapid peak plasma levels allow for this

• – This is generally a good thing except for those patients who cannot absorb medications in the GI tract due to a shortened tract or malabsorption syndrome

Slow-release products extend the natural half-life of most drugs and may sometimes lower inter-dosing withdrawal effects

Generally, the slower the release mechanism is, the more likely the drug may be employed as a once-a-day drug, thus improving compliance

Pharmacoeconomic and regulatory moment

Slower-release preparations are often more costly as the drug manufacturer has to pay for the development of the immediate-release drug itself and also pay for the development, or patent use, of the slow-release mechanism that surrounds the molecules of the immediate-release drug. This way, there are two costs for one drug

The FDA allows for approximately 20% bioavailability differential between original brand name drugs and their generics

• – Generally, this is not a problem for most patients, but some will be more sensitive and gather more side effects if the generic is 15% more bioavailable

• – Some patients will relapse if the generic is 15% less bioavailable

• – The slow-release technology between the brand name and generic drugs may also be different in bioavailability

  • Therefore, a generic slow-release drug may have two generic properties

    • The generic drug itself

    • The generic slow-release mechanism

  • If the generic slow-release mechanism allows faster release than the brand name, new side effects may appear when the brand is changed to generic, as peak plasma levels occur faster and to a higher concentration

  • The FDA has alerted prescribers that extended slow-release bupropion and slow-release methylphenidate (osmotically controlled-release oral delivery system [OROS]) generics are, in fact, different pharmacokinetically from the brand name version, as examples

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