Wednesday, November 7, 2012

Cymbalta (Duloxetine)

Cymbalta is one of those truly breakthrough psychiatric medications. There is a tendency for pharmaceutical companies to produce a lot of 'as likes' or some medications that may well be 'new" but don't offer alot of advantage over previous medications.

In the antidepressant class of medications the tricyclic antidepressants (amitriptylline, imipramine, clomipramine) were surpassed by the advent of the Serotonin Specific Reuptake Inhibitor, Fluoxetine or Prozac. This remains a powerful and amazing antidepressant with anti anxiety and anti obsessive compulsive properties. What it provided over the tricyclics was earlier onset of action and benefit, less chance of lethal overdose and amazingly fewer side effects.  The class of SSRI's expanded with a variety of essentially 'as like' SSRI's each with some benefit and specificity but none with the 'breakthrough' significance of Prozac.  The latest of this class is Cipralex and it's advantage over the originator of the class is even less side effects, more specificity for anxiety as well as being equally good for depression.

What all the newer SSRI's had was a shorter 'half life' in the system. This means that they were metabolized faster and didn't build up in the system.  The build up of Prozac in the system is actually a god send in conditions like Obsessive Compulsive disorder where this is desired but it can also increase the risk of Serotonin Syndrome, an extremely rare almost non existent complication of the newer SSRI's. I've seen only a couple of cases in my years of experience and neither was a significant concern responding to appropriate treatment and a consequence of multiple factors beyond the actual SSRI treatment.  Because the condition, like a servere allergic reaction to a medication, can be lethal it is still taken very seriously, even though Aspirin may present more overall lethal "risk" than SSRI's.

Cymbalta though is what is called an SNRI.  Effexor (venlafaxine) is the best known of this class and followed shortly after the advent of Prozac.  SNRI means Serotonin Noradrenaline Selective Reuptake Inhibitor.  Both Serotonin and Noradrenaline neurotransmitters have been proven to be instrumental in the well functioning of the emotions and mind.  Their 'deficiency' is associated with depression and work with brain 'pacemaker' implants suggests that they may well become 'deficient' because as patients describe their "minds won't shut off' and they 'can't stop worrying'.

The advantage of SNRI's is that they're broad spectrum.  Effexor tended to help a broader range of patients from the get go and because it came in a low dose form, 37.5 mg it could be started at low dose with the least concerns for side effects.  The down side of Effexor in my experience though is that it gained the name 'side effexor' because of a tendency to have increasing side effects with higher dosages than 150 mg, which indeed was the industry recommended upper limit of the medication. I've used 225 mg personally with patients and only had side effect concerns when I'm combining antidepressants with other in resistant cases.

In the famous Star D protocols, the classic study of antidepressant medications with adjunctive medication in resistant chronic depressive populations, Effexor was a comparison drug with Celexa, the precurser of Cipralex.

Cymbalta though being an SNRI is a break through medication. It is the first of the antidepressants since the trycyclics to be specifically effective with what was historically called 'somatic depression'.  It's been studied and found highly beneficial for 'on label' use with peripheral neuropathy, diabetic neuropathy,  fibromyalgia, conditions called 'pain disorders' or 'complex pain disorders'. Indeed it appears to help any pain disorder associated with depression.  It is therefore not only a highly effective antidepressant and a broad spectrum anti anxiety medication ,it's also is specifically beneficial for the treatment alone or as an adjunctive for pain disorders.

When I worked on cancer wards I commonly combined an antidepressant with whatever standard pain killers we were using, whether it was NSAIDS or narcotics, this was all 'off label' and empirically done based on clinical experience. Cymbalta however is 'on label' medication for somatic pain, especially fibromyalgia.

In my practice I have seen amazing benefits with cymbalta, patients noting partial or wholly relief from horrendous and terrifying pain conditions, often associated with severe motor vehicle or work place injuries.  They come in and spontaneously tell me that the medication is the first medication that has given them real relief.  This makes a clinician's heart soar as often treating psychiatric disorders, especially chronic disabiities, is an uphill hard won battle done a day at a time slowly. Patients report being equally pleased with it's antidepressant propertites and especially with it's anti anxiety effects.

The side effect profile for cymbalta has been much the same as effexor or any of the SSRI's in general. People complain of the standard nausea and gi upset and some complain of headache.  These tend to go away in a few weeks. The medication is taken with meal time and I start it at 30 mg every other day building up to 90 or in some cases 120 mg.  Patients have had significant benefit at 30 mg, though 60 mg seems the 'sweet spot' for the medication. There's unlikely much benefit to be gained by increasing the medication beyond 120, in my clinical experience.

All antidepressants, especially the tricyclics , and certainly the MAOI's inhibitors before them have been stopped by patients because of 'uncomfortable' side effects.  Often this is worst with highly 'suggestible' patients who read the inserts, 'study the internet', and listen to their clinically ignorant young pharmacists who are notorious for inducing 'nocebo' reactions in psychiatric patients.  I have had a patient have 'every' side effect for 'every' medication I've given him. I'm thankful to have worked with cancer patients and with patients with HIV, kidney or heart disease, because the medications we've used in these cases all have side effects but the patients are much more willing to 'tolerate' the medications than some of the psychiatric patients who claim to be 'sensitive' to medication.  I don't even bother assuring them that immunologically suppressed patients are extremely 'sensitive' to the side effects of patients but they are simply much more motivated to get rid of their illness even if it is associated with initial suffering.  Having started out in surgery I know all my patients had horrendous side effects from surgery and were commonly sick for days or weeks after but this rarely stopped them from all manner of procedures for all manner of reasons.

Thankfully Cymbalta like the rest of the SNRI and the SSRI class have few side effects which commonly go away.  The headache and light headedness to the best of my clinical experience seem to be an effect of the medication causing a person to underestimate their need for fluids. If patients drink more fluids than they think they should the headache and light headedness seem to depart quickly.

I've only seen sexual dysfunction in one patient so far but then that patient was sexually dysfunctional before the medication and has complained of sexual dysfunction with every medication.  My suspicion, in fact, is that they would be sexually dysfunctional on viagra but to date I've discretely refrained from suggesting this.  In contrast other patients report remarkably improved sexual desire and performance.

Whereas the SSRI classes have been associated with bizarre thought process I've only had one patient whose thinking was disturbed by Cymbalta.  Indeed patients report improved concentation, attention and memory with cymbalta and this was what was noted in the vast majority of patients with Prozac initially when it was really popular with the computer programmer genius set.

Cymbalta hasn't been around long enough to build the track record of Prozac but to date it really does look like it will continue to be a truly amazing new breakthrough in medication.

No comments: