Showing posts with label prozac. Show all posts
Showing posts with label prozac. Show all posts

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.

Sunday, January 1, 2012

Cymbalta (duloxetine)

Cymbalta (duloxetine) is a new serotonin norepinephrine re uptake inhibitor (SNRI) antidepressant medication developed by Lilly Pharmaceuticals.  After the Tricyclic medications which were the first truly effective antidepressant medications which came out in the early 50's, prozac became available as the first of the Serotonin Specific Reuptake Inhibitors (SSRI's)..  Subsequently antidepressants like Effexor were developped which worked on both the serotonin neurotransmitter pathways and the norepinephrine neurotransmitter pathways.  Cymbalta is not there fore the first SNRI.
What it is however is the first of this class of medications which has FDA approval for pain disorders.  Prior to this amitryptalline, a tricyclic antidepressant was the treatment of choice for fibromyalgia for instance.  However patients commonly complained that they only had limitted benefit and the tricyclics have alot of hard to tolerate side effects.  The side effects in general assocaited with all the new antidepressants are mostly annoying and not particularly dangerous. The tricyclics however could cause heart failure.
Cymbalta in contrast is a major breakthrough and relatively safe with much fewer side effects than those early antidepressants. Already it has given many patients improvement in pain which they did not have from any non narcotic agents. .
Naturally when a new medication is developed the pharmaceutical company would like everyone to switch to this medication. Medications are like cars in this regard.  Commonly family physicians and psychiatrists are given 'free samples' to help start patients on the latest medication.  This is a marketting strategy but it's also a very valuable clinical tool. Commonly in psychiatry a patient may have to try more than one medication before that which is most effective is found. Each time they fill a prescription they are charged the full amount even if they can't tolerate the medication or it's ineffective and they stop it aftera a few weeks. Free samples allow a patient to try a medication without cost to them and if it works without negative side effects then they can fill the prescription.
I have some patients who are still taking the original tricyclic medication prescribed to them 30 or more years ago. It worked then and it works now. Several other patients responded to later SSRI's called Paxil and Zoloft.  They benefited from these medications when they had their first bout of depression, recovered and stopped the medication only to have the depression occur 5 or 10 years later. I tend to try the medication that worked for them before in the hope that they will benefit from this once again. It's not disimiliar to antibiotics in that way.
Roughty 75% of patients with depression or generalized anxiety will respond to whichever antidepressant you choose first time.  Of the 25 % non responders, roughly 75% of them will respond to the second line choice.
When I worked in the states patients without plans would ask for the cheapest medications and I'd be able to know the oldest cheapest antidepressant would do the trick but the side effect profiles were a concern. Not unlike cars, the shocks on the old ones aren't what they are today.  Prozac was a break through in medication as compared to the tricyclics and MAOI inhibitors because it was hard to kill yourself with it.
The newer antidepressants collectively have a safer profile and overall improved side effect profile.  The antidepressants compared to most medications are very safe.
Cymbalta is effective for generalized anxiety disorder and depression.  So normally a specialist, especially a consulting specialist will see the 'non responders'.  There are patients in my practice who have simply not got better with any antidepressant medications and have been sent to me. This is where cymbalta is the 'first line choice of medication. I am truly happy to say that I have already seen Cymbalta work with non responders.
Further, people who had less than complete results with trials of several of the other classes of antidepressant medications have had excellent response to cymbalta.
Also benefitting are those people who have chronic depressions or anxiety disorders and whose medications seems to wear off after a year of two requiring higher dosage with increasing dose related side effects. These people tend to respond immedidately to the lowest dosage of an untried antidepressant medication, like Cymbalta.
What is offensive in psychiatry and why good universities demand that psychiatrists working for drug companies declare their bias is when these 'trend setters' make unreasonable claims for a new medication.  These colleagues get called 'drug company whores'as a result.  For instance they might say some new medications has a 95 % success rate with depression or suggest that patients already responding well to an earlier antidepressant medication should suddenly switch to the newest and more expensive medication.  For this sell out they get a trip to Hawaii or help getting up the academic ladder.
The fact is Cymbalta has something the other medications don't have and for that reason is my first line choice when I'm treating a combination of either a generalized anxiety disorder or depression with a pain disorder. My patients especially the older ones with traumatic athritis and those with fibromyalgia and even a patient with migraines have reported significant improvement in their pain as a result of starting cymbalta.
This happened when I gave wellbutrin, also marketted as zyban, to smokers with depression, a number of them found it easier to quit somking. Hence if I have a patient who wants to quit smoking and has depression I would consider well butrin as a first line treatment.  Wellbutrin is also called buproprion and has been used successfully extensively in addiction psychiatry.
Cymbalta now is the new drug of choice for that mixed state where pain and depression or anxiety prevail.  I love scientific advances in psychopharmacology and this truly is.  My fibromyalgia patients are especially pleased with it's benefit.
The side effect profile is roughly the same as effexor with some nausea and possibly tendency to make one sleepy.  The key is starting the medication at 30 mg and slowly titrating it upwards to the best dose for the patient, which so far in my practice has been in the 60 to 90 mg range though it's likely to be beneficial at double this dosage or it may turn out there's a window between 60 and 120. It's too early to tell but responses are being noted in the early weeks at as low as 30 mg which was what we saw when we started using prozac and 10 mg to 20 mg was sufficient.  Later we learned that obsessive compulsive patients often needed 60 to 80 mg and it's possible there will be a subcategory of patients who need higher dosages of Cymbalta. For now I'm just really thankful to Lilly for providing a product that is such a breakthrough.
Pharmaceutical companies spend millions and millions on research and development something the 'health food industry' is not in the habit of doing.  Consider the making of a new Hollywood movie with all the jobs and all the new ideas and compare that to late night 're runs'. That can be said for alot of 'alternative medicine'. Yes I know their are exceptions but I think people forget that these are 'big business' too and don't appreciate the contributions that are provided by the pharmaceutical industry.
Almost all my patients have tried 'everything' when they get to me.  I am thankful for all the help I can get. Cymbalta is just that kind of help. Lilly is a great pharmaceutical company that has done amazing research and provided great breakthrough in medications. Thank you, Lilly.