Monday, August 21, 2017

Psychopharmacology for Depression (idiot's guide to CANMAT)

The following is an off the cuff review of my clinical experience.  I have this information available for me and it forms the basis of my treatment plan before I consult CANMAT.  If I was a new doctor I might look to CANMAT earlier rather than later but I've seen and treated thousands of patients so use my clinical experience first. If something goes wrong, I, not CANMAT, will be faced with the consequences .That said CANMAT produces great tools.
Also if you have any question about particular medication I've found that the manufacturers are an amazing resource.  A lot of the internet information is not.  Much of the information is false and put forward by competing interests.  CANMAT and the actual manufacturers are the best resources.

1. Depression - there are a variety of antidepressants which fall into the following principle categories.
A. MAOI's - I've only used these a few times in the last 30 years. They were highly effective but their problem was interactions with other drugs and certain foods.This could lead to a hypertensive crisis.
B: Tricyclics - these were the mainstay of treatment when I began. The first was amitriptylline and imprimane.  We don't hear much of imipramine these days but amitriptylline is still used widely. It's specific benefit is at low dose (under 10 to 50 mg ) it's a very effective sleep medication. It's other advantage is that it's very helpful with chronic pain, chronic fatigue and fibromyalgia.  One theory is that amitriptylline improves the depth and quality of sleep and hence reduces the anxiety and pain.  These were introduced in the 1950's and one of the main reasons for the reduction in stays in asylums.  Depressions untreated could last 1-2 years and the efficacy of the tricyclics was that within 6 weeks people could be functional again without depressive symptoms.  Medications were recommended in general from 1-2 years.
Norptriptylline and Desipramine are the second generation tricyclics which still are used not uncommonly in the treatment of depression especially when the depression is diagnosed as 'atypical' or when the SSRi and SNRI's have been used and tricyclics are consdered next.
These second generation tricyclics have fewer side effects.
The principle side effect that people complained of was dry mouth.  Also low blood pressure with standing quickly.'The side effect of urinary retention has lead to tricyclics being used still in the elderly where night time urinary incontinence can be a problem.  The limitting factor was that with overdose they could cause arrhythmia and patients who overdosed had to be followed in ICU or at least on a heart monitor for a few days.
The tricycles start at 10 mg and are used up to 300 mg without compounding medications or conditions if necessary in the treatment of depression.
C: SSRI - the first SSRI was fluoxetine or Prozac.  The real advantage of the SSRi was that there were far fewer side effects, that they could be used more safely with other medications and that they had to be taken in very large amounts to cause suicide.
Prozac was introduced in the 80's.  Since then there has been ongoing studies of the children of mothers who received Prozac and they've shown very very few side effects, perhaps some increased anxiety.  That makes the SSRI class one of the safest medications in history, certainly safer than alcohol.
Fluoxetine (Prozac) was begun at 10 mg and could be increased to 60 mg. I've used 100 mg on patients with OCD.  I continue to maintain Prozac is the treatment of choice for OCD.  It was a better anti anxiety medication than tricyclics in general.  Anxiety and depression thought to be different conditions often overlapped and the antidepressant medications are commonly the mainstay in the treatment as of chronic depressions and chronic anxiety disorders.
The SSRI"s are considered the mainstay treatment of choice for  chronic Panic Attacks as well.
Second generation SSRI's included the following medications:
Sertraline or Zoloft - used 25 to 150 mg - this was a very good antidepressant but it quickly became the treatment of choice for PTSD and later for Social Anxiety.  It remains a very well tolerated and well liked SSRI.  The advantage of the secondary and later SSRI's was their shorter length of action in the system.  Prozac had a long half life (half life the metabolism of a drug, the longer the half life, the more in the system, the shorter the half life the more quickly a drug is cleared from the system).  Prozac could build in the system without us knowing and while this was beneficial in the treatment of OCD which is resistant to treatment it could lead to Serotonin Syndrome which is much worried about these days.. (I"m less anxious about Serontonin Syndrome since I've actually treated several cases when I worked in the asylum and only saw it there where we were using experimentally high dosages.)
Fluvoxamine or Luvox was another second generation SSRI. I simply didn't use a lot of this in practice but my colleague favoured it as a good antidepressant.
Paroxetine or Paxil - used at 20 to 40 mg - was an especially popular medication for depression, anxiety and anxious depressions.  The problem was that it had the highest sexual side effects of all the SSRI's.  The sexual side effects were loss of interest, elective failure, lubrication loss and lack of potency. 40% of patients in one study complained of this but only if asked.  Interestingly Ginkgo Biloba counteracted most sexual side effects. Viagra and cialis counteracted the sexual side effects of the SSRI's but not just for men but for women as well. My female patients told me they just said it was for their boyfriends (wink, wink).
Now I don't know why but Wellbutrin or Buproprion an atypical SNRI. (Works on Norepinephine and Dopamine)  , the only elevating antidepressant, worked as well to counteract the sexual side effects of Paxil.  Combining Wellbutrin with an SSRi also addressed the fatigue some people described with an SSRI
About half the people took the SSRI's in the morning in comparison with the normal evening dose of tricyclics.  However when Wellbutrin or Buproprion was used this was taken in the morning and the SSRI in the evening.
Trazadone (?Oleptro) is an SSRI that is principally used for insomnia.  It was at first an antidepressant and was very effective as an antidepressant at 300 to 600 mg dosage however patients found it to be a terrific sleep medication in the 25 to 200 mg range, most commonly at 50 mg.  It caused too much 'hang over' and sedation for most people. Today it's particularly special effect is that it can be used in combination with all other SSRI or SNRI's where insomnia is a major problem. This way it boost the antidepressant being used and addresses the sleep disturbance.
Third Generation SSRI
These are Citalopram (celexa) and Escitalopram (Cipralex). These are the latest SSRI's and have the advantage of shorter action, less side effects and amazingly safe use with other medications. Hence if I had an elderly patient with heart disease, diabetes and COPD with depression I was scared to start a tricyclics or even Prozac because of it's long action but I've been using Celexa and Cipralex extensively and safely in these complex medical cases. Citalopram or celexa is a better antidepressant than antianxiety drug, while escitalopram is a better anti anxiety drug.  Both start at 10 mg and can be increased to 30 or 40 mg. I've got one or two patients on more but it's generally not recommended.
When asked when to change a medication to another medication because the first doesn't appear to be working I like to use at least 1 1/2 times to 2x the recognized dosage of efficacy before saying a medication doesn't work.  Hence I'd use at least 30 to 40 mg of Citalopram before considering I'd had a worthwhile trial.
I start low with medication using the reccommended or half the recommennded dosage of the medication initially. I expect to see benefit in 2 to 4 weeks and would increase the medication on an outpatient basis, in the community at 4 to 6 weeks if the patient isn't getting better. However if the patient is improving I will go slower with the dosage increases definitely.
SNRI - Serotonin Norepineprhine Reuptake Inhibitors
Venlafaxine or Effexor is the first generation SNRI.  It's also been called 'broad spectrum'. It has very good antidepressant and anti anxiety benefits and I've seen it used superbly in the general practice for patients with mild to moderate depressions requiring medications.  It's problem for me personally is that as a specialist I get patients coming to me when the medication, which starts at 37.5 mg effectively is slowly increased to the maximum 225 mg range. Past 150 mg my tendency is to call this medication 'side effexor'.  Alone it is an amazing medication and it can be augmented really well but it interacts with other medications and in contrast to the SSRI's where higher dosages can be achieved, the side effects with venlafaxine increase in a hockey stick curve, anecdotally, clincally, after about 150 mg.
The STAR D Protocols which are very much written about were an amazing study of chronic depression and they compared two streams of patients with the SSRI Celexa in one and the SNRI in the other stream.  This is an essential study for anyone doing long term psychiatric treatment in the real world. The clinicians involved were the finest and the questions raised and addressed were the bread and butter of psychiatric practice.
The Star D protocols used a variety of augmentation strategies.
Buspirone - Buspar - this is an atypical anti anxiety agent like Valium or Ativan without the addiction potential.  In my practice about a third of patients I 've prescribed it to have sworn by it. It can be used at 10 mg a day to a maximum of 10 mg four times a day.  It was used to augment the antidepressant in the Star D protocols once one had achieved the maximum dose one was going to use, approximately 1 1/2 to 2 x the standard dose.
Thyroxine or synthroid was another augmenting agents in the STAR D protocol studies
Stimulant medications such as Ritalin or Dexedrine in low dose are also used to augment anti depressants where the patient has a history of head injuries, the medication side effect is weight gain which is not wanted,  and where the patients depression is associated with a lot of neuro cognitive symptoms like lack of concentration.
Atypical antisychotic augmentation is commoner these days as increasingly people are diagnosing Bipolar Spectrum and Bipolar II disorders which tend diagnositically overlap with the traditional Major Mood Disorder Depression or Unipolar Depression or the traditional Anxious depression.  The principal low dose atypical antipsychotics used are Seroquel, a very good sleep medication, in the range of 25 to 100 mg in combination with an anti depressant, rispiridone .25 to 1 mg of or ariprazole or ability 2 to 5 mg od.
It should be noted that the atypical anti psychotic or major tranquilizer class of medications including those named plus olanzepine are the mainstay treatment of Bipolar II and Bipolar Spectrum treatments.
The antiseizure drugs such as Valproic Acid, Divalproex, Carbamezapine or Tegretol, and Lamotrogine or Lamictal are perhaps today considered second line treatments or to be used in combination.
Diagnosing Bipolar II instead of Unipolar Major Mood Disorder makes matters a whole lot easier for the clinician because almost all of the pharmacopeia of the psychiatrist can be used in the treatment of Bipolar II.
I'm called upon to 'rationalize' and reduce the overall medications used in some exuberant prescribers.  When this occurs I try to use different classes of medication before using three or four of the same class.  Further I consider the medication choice by the presence of other symptoms and choose a medication where the side effects of the medications can be beneficial for the patient.  Recently I used a tricyclics as my first choice of medication because the patient had urinary incontinence. Normally my first choice would be an SSRI.
Duloxetine or Cymbalta is a unique SNRI.  It's an excellent antidepressant.  It's also been studied for the treatment of fibromyalgia and chronic pain. It's an amazing drug.  Commonly Amitryptylline at low dose was all we had for chronic pain conditions now called by DSM5 Somatic Sympton Disorder but duloxetine came along and has far greater benefit without the side effects.  It's started at 20 mg and increased to 120 mg with most people finding 60 mg effective.
The term 'somatic depression' was commonly in use in the past to refer to conditions such as chronic pain and lethargy and a variety of depressions where the person felt bad but didn't really 'think' bad. It wasn't like the person was saying to themselves I'm hopeless but I just feel awful instead. This was where Cymbalta was a true breakthrough.
All SSRI and SNRI's have an initial side effect of some indigestion and nausea.  There are a variety of ways to counteract this. First start at the lowest dose, take every other day at first , use ginger and lots of fluids and slowly increase.
Vortioxetine or Trintellix is the latest of the antidepressant which seems to be the latest  atypical SSRI.  It specifically antagonizes  5-HT3 receptors while agonizing 5-HT1A receptors. The outcome is that it's an extremely good antidepressant but it really works on those depressions where people have cognitive concerns such as decreased concentration and memory. It also is specifically marketed for those people who have a successful response to antidepressants in the first year but describe not feeling themselves again, that they're specifically cognitively not where they were, in terms of motivation and ability to do computer or office work. It seems to enhance thinking and my patients have found it superior in this way. This has been an antidepressant that my academic patients , professors and such have found highly effective for them.
Des venlafaxine or Pristiq is the latest atypical SNRI. It's the broadest spectrum of antidepressants and appears to be an advanced Effexor without the side effects. It has a window of benefit in the 50 to 100 mg range with not noted benefit with increase.  It's amazing for it's tolerance in general by patients, and the lack of side effects. Like Effexor it really helps with the patients who have a mixed anxiety depression picture. I've only had good feed back but have limited experience with it as it's more commonly used by those seeing first encounter cases where it 's broad spectrum benefit helps with ensuring that patient get early response.

CANMAT is the Canadian Network for Mood and Anxiety Treatments. The organization puts out guidelines for treatments and the 2016 CANMAT Guidelines are excellent.  Since my all time favourite mood disorder genius Dr. Solomon retired recently I have found myself looking at the CANMAT guidelines directly not being able to phone Dr. Solomon and ask him what to do when I've been stymied. These Guidelines are amazing if a bit more complicated than what I've indicated. They are an essential for anyone treating psychiatric patients.

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