Why and how does Anafranil work for Pure O?

[EclecticJoe]

If it hits both serotonin and nor epinephrine in the brain and that is the key to it's mechanism I ask the following:

1. Why don't other SNRIs work as well for Pure O or do they?

2. Why couldn't you combine a SSRI with a low dose stimulant like Dexedrine or Phentermine to achieve similar results without the nasty side effects like weight gain?

There has been studies showing Dexedrine to work in certain cases for OCD and anxiety, a paradoxical effect.

[insights]

If it hits both serotonin and nor epinephrine in the brain and that is the key to it's mechanism

Its effects on norepinephrine/noradrenaline (NA) may not be the key to its success, but the total package probably is. Anafranil actually is among the most potent serotonin re-uptake inhibitors beating even most SSRIs by a considerable margin. Its affinity for SERT transporters is 0.14 Ki, with SSRIs falling in the range 0.1-20 Ki (lower is more potent) and is probably the only antidepressants that is clinically a true SNRI (Gillman PK, 2007, Abstract, Full text). Others are clinically either SSRIs or NRIs. 

It is also probably the most potent antidepressant, which may also contribute to its effectiveness. OCD tends to be the most treatment resistant of the anxiety disorders, both to drugs and therapy, and part of the problem with drugs just may be that at the doses most antidepressants are prescribed they just aren't strong enough to affect OCD.

1. Why don't other SNRIs work as well for Pure O or do they?

Venlafaxine (Effexor) is a weak NRI, with a NA inhibition of 1420–6300 Ki compared to 54 Ki for clomipramine. Duoxetine (Cymbalta) is good on both serotonin and especially norepinephrin, so may be worth trying, however, it is still weaker at inhibiting serotonin re-uptake than clomipramine, 0.8-3.2 Ki compared to 0.14 Ki.

2. Why couldn't you combine a SSRI with a low dose stimulant like Dexedrine or Phentermine to achieve similar results without the nasty side effects like weight gain?

A stimulant? <shock, horror, swoon>!  The anti fun police would go ballistic. 

There is also this: fen-phen. It would be a very, very brave pharmaceutical company that touched a serotonergic/stimulant combination, even with a humongously long barge pole.

Ian

[EclecticJoe]

It's funny how for pure O different PDOCS swear by different things. Some say SSRIs are the best, some say mood stabilizers or AEDs are the best, a few use anti psychotics, and a few more try SNRIs or even some weirder combo. Its like they get locked into a treatment mode and no two are alike.

[stevo1111]

More often than not they seem to go with whatever they have had the best luck with. My Dr, although he is an old timer, has recently only used the SSRIs and insists on them as a first line, second line and third line treatment for EVERYTHING that has to do with your mood.

The obsessional type anxiety disorders tend to be the hardest to get under control, in my book I lump panic disorder into there. So they need the strongest anti-depressants to knock them down. All be it my opinion, it seems that these nasty anxiety disorders need the hammer, Anafranil, to knock them down to a tolerable level.  Having taken 25mg for a few months, and at one point going up to 50mg, it is assuredly strong. For comparison, a 25mg Elavil might as well be a nice sleeping pill for me, at 50mg of Anafranil I was as flat as at the higher end therapeutic dose, 20mg, of Lexapro.

There had been some studies showing Effexor is as good as Anafranil with less side effects, but I am yet to see empirical evidence. If you're in a rough enough spot to need to go to Anafranil, you need something powerful.

If you can't function, Anafranil is likely the answer. If you can get yourself through the day but it's tough, then Anafranil probably ought to be kept on the back burner. It knocked me down a few notches and it just wasn't worth the gain, although I never made it to the therapeutic dose... so maybe I missed out on something.

[hurvinek]

I use Anafranil 250mg before bedtime and 150mg seroquel at bedtime.
I am a big guy and I still wonder if it is enough.
I suffer from frequent health (cancer) anxieties and currently i am battling a fear for cancer.
had several test everything negative. I am having a really hard time and i am wondering If anybody has experience with higher doses of Anafranil then 250mg???
anybody would recommend certain meds for strong health anxiety???

[insights]

If anybody has experience with higher doses of Anafranil then 250mg???

Not Anafranil, but I was on 350mg of imipramine (Tofranil), which is 50mg over the inpatient maximum, for over 6 months at one time, so you might be able to tolerate 300mg of Anafranil in 3x divided doses, provided you don't have heart disease which would preclude this. If your doctor is willing to push the envelope, and most probably won't, then I suggest you have regular EKGs/ECGs, initially weekly for a month followed by monthly for a while just to be sure the electrical system of your heart is not being affected.

However, before increasing the Anafranil dose I suggest you try supplementing it with Buspar (buspirone) first. Buspar has shown promise in boosting the effectiveness of SSRIs when the maximum dose don't quite cut it and there is no reason why is shouldn't also do so with a TCA. It may also counter some of the ongoing Anafranil side-effects such as sexual dysfunction.

Ian