Amphetamines for depression?

[Funniman250x]

Though I am only a pre-medical student as of now I have endulged myself in the realm of psychiatry and have a question if anyone is interested in answering. I was reading up on the history of psychiatric medicines and stumbled upon the use of amphetamines for depression in the 1920's. My question is whether or not amphetamines are used today for depression and/or are they used in combination with SSRI or SSRNI's to combat a lack of attentiveness that is associated with these medications in certain people. Personally not me, but reading cases where people are in school faced with depression and still trying to do well in their classes. Though these drugs are not contraindicated can there be undesired side effects such as hypertension and irregular heart ryhthms which will deter a psychiatrist from prescribing this combination of drugs? Is there are alternative to amphetamines in this case? I am extremely interested in psychiatry and even though I am currently a Paramedic and people assume I would love to go into Emergency Medicine, psychiatry is where my heart lies. Thank you in advance for any input on this subject.

Jeremy Cerce

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[tennreb]

I frequently prescribe stimulants such as Provigil and Adderall as augmentation therapy with SSRIs/SNRIs for depressed patients, especially those with anergia and anhedonia. I've found it very useful in the geriatric population.

 

[Funniman250x]

Now say for instance you diagnose that patient with insomnia due to disorders such as sleep apnea etc. Would these stimulants, even taken early in the morning when one starts their day, affect their ability to sleep? I know that SSRI and SNRI's have a tendendy to disturb REM sleep so how could they possible attain quality sleep? Would you prescribe a medication such as Lunesta to counter these effects? and if so where are the limits of prescribing numerous medications to a patient? I apologize if I am asking what seems like a million question this is just very interesting to me!

 

[tennreb]

Now say for instance you diagnose that patient with insomnia due to disorders such as sleep apnea etc. Would these stimulants, even taken early in the morning when one starts their day, affect their ability to sleep? I know that SSRI and SNRI's have a tendendy to disturb REM sleep so how could they possible attain quality sleep? Would you prescribe a medication such as Lunesta to counter these effects? and if so where are the limits of prescribing numerous medications to a patient? I apologize if I am asking what seems like a million question this is just very interesting to me!

It depends on the half life of the particular medicine and the time of day you dose it. If dosed correctly, a stimulant should not have too much effect on sleep. However, it is sometimes not possible to do so. It's usually not a good idea to add more medicines to cover the side effects of medicines a patient is taking, but it is often necessary. On rare occasion I'll have a patient on both stimulants and a sleeping medication.

 

[whopper]

Some psychiatrists use an amphetamine augmentation strategy for people with severe and vegetative depression.

Amphetamines do help depression, but obviously you got to worry about the risk of abuse and dependence.

If they are used, the one responsibly method I've seen is to use it only for a few days to weeks maximum. Put them on another antidepressant, and by the time the other one should start taking effect, wean them off the amphetamine.

There is some data on this in journals, but I don't remember the last time I've read anything on it.

These days, I'd rather give a non-amphetamine stimulant. I've rarely seen any cases that IMHO were to the extreme where I'd consider it. The one time I've seen amphetamines used was on an individual with vegetative depression to the point where she did not want to get out of bed. With the medication, the same day she was up and moving around. Ironically, the doctor that prescribed it never gave out benzos except for alcohol or benzo withdrawal. When he decided to give it I figured there must be something to it.

 

[michaelrack]

I know that SSRI and SNRI's have a tendendy to disturb REM sleep so how could they possible attain quality sleep?

1. The importance of REM sleep is over-rated

2. The REM-suppressing effects of antidepressants tends to decrease over time.

3. The SSRI's are somewhat disruptive of sleep. Hypnotics such as Lunesta can be helpful. This has nothing to do with REM sleep.

 

[J ROD]

Check out Wellbutrin!!!

 

[kugel]

1. The importance of REM sleep is over-rated

That's an interesting statement. Care to elaborate?

 

[watto]

I would be hard-pressed to identify any specific cases I've seen where I have had patients with PSG-verified decrements in REM that correlate with neurobehavioral complaints. Sure, in research you can always pinpoint outcomes if you are looking for them (with vigilance tasks and, though it is controversial, certain tests of emotional memory), however in practice I have not seen it.

More notable is the link between wake time after sleep onset and subjective fatigue / malaise -- as well as reductions in NREM delta sleep expressed as either discontinuity in the normal progression of sleep stages or as awakenings from delta sleep due to arousals. Those people tend to complain of a lot more daytime impairment (again, in my experience).

I recommend one of Jerome Siegel's great articles on the phylogeny of REM sleep, where he reviews the debates over its evolutionary benefits. It was in Nature a few years back.

 

[whopper]

I don't know if it's overrated.

I do know studies were done to prevent people from getting REM. They were allowed to sleep in a sleep lab. Right when they entered REM, they were awoken. This occurred for several days. After some time, most people started having several problems such as illusions, problems concentrating and several others.

I've sometimes wondered if excessive REM is linked to depression. One of the older, pre-antidepressant treatments for depression was sleep deprivation. SSRIs reduce REM. Could that be one of the mechanisms by which it decreases depression?

As for Wellbutrin, the data suggests that it does not affect REM, or at least affect it as much as an SSRI. From the data I've seen, however, I don't think much data was obtained on wellbutrin's effects. I've seen very few studies on it, and of the ones out there, the biggest group had twenty people.

If my understanding is correct (and it might not be--maybe there's more studies I missed), than I do think more data needs to be obtained before we psychiatrists conclude that Wellbutrin has little effect on REM.

And it would make a specific PRITE question concerning this area invalid. IMHO you need more than a few studies, the most with 20 people before you're going to make a PRITE question where the correct answer states Bupropion has the least effect on REM. With a sample size that small, you might as well start throwing in questions where the correct answer states that increased LDL reduces risk of heart attack or stroke.

 

[watto]

I don't know if it's overrated.

I've sometimes wondered if excessive REM is linked to depression. One of the older, pre-antidepressant treatments for depression was sleep deprivation. SSRIs reduce REM. Could that be one of the mechanisms by which it decreases depression?

So monoamines inhibit REM-on cells. I am oversimplifying, but if someone has, say, fewer monoamines there to do this, you might predict that there would be less inhibition on these cells and hence, more REM. That is the mechanism by which antidepressants tend to reduce REM.

 

[whopper]

So monoamines inhibit REM-on cells

You need to be careful with this. Dopamine (or at least Wellbutrin which is a Dopamine-RI and an Norephinephrine-RI, but not an SSRI) in studies showed it did not affect REM or actually increased REM (depends on the study), but again, those studies had small sample sizes.

Dopamine and Norepinephrine are monoamines.

The effect of specific neutrotransmitters on sleep is not well understood. An SSRI for example could decrease REM, but why does it do that? It could be for a multitude of reasons we do not yet understand.

You, however, are thinking along the guidelines that any good psychopharmacologist would do-on the neurotransmitter level.

 

[watto]

Bah, who knows with WBT - as you mention, it could be one of many things or it could be the sample. The animal research is pretty extensive on at least mammalian sleep...also, any discussion of REM sleep should address acetylcholine, which is at near-waking levels during.

I would say we know a heck of a lot more about the mechanisms of the MAs than we do about, say, orexin right now (also postulated to have mood-enhancing effects...though again, in animal models).

 

[OldPsychDoc]

You need to be careful with this. Dopamine (or at least Wellbutrin which is a Dopamine-RI and an Norephinephrine-RI, but not an SSRI) in studies showed it did not affect REM or actually increased REM (depends on the study), but again, those studies had small sample sizes.

Dopamine and Norepinephrine are monoamines.

The effect of specific neutrotransmitters on sleep is not well understood. An SSRI for example could decrease REM, but why does it do that? It could be for a multitude of reasons we do not yet understand.

You, however, are thinking along the guidelines that any good psychopharmacologist would do-on the neurotransmitter level.

But you also need to think about this as a neuroanatomist and neurophysiologist. The brain is not the liver. Sleep involves the hypothalamus (histamines, peptides), reticular nucleus of the thalamus (GABA), reticular activating system (glutamate & ACh), locus ceruleus (NE), and raphe nuclei (5HT). Most of these neurotransmitters are acting presynaptically on inhibitory autoreceptors as well as postsynaptic receptors that modulate both activating and de-activating second messenger cascades (and thus eventually gene transcription). It is NEVER about the "levels" of this or that neurotransmitter...

 

[whopper]

Most of these neurotransmitters are acting presynaptically on inhibitory autoreceptors as well as postsynaptic receptors that modulate both activating and de-activating second messenger cascades (and thus eventually gene transcription). It is NEVER about the "levels" of this or that neurotransmitter...

Exactly.

Several circuits in the brain are rarely a simplistic--one thing makes another thing more or less--and there you have it.

A neurotransmitter can make certain things more or less along the same tract, and when a psychotropic medication is introduced, it works essentially globally--throughout the brain. In terms of it's effect on the patient, we only see the sum totality, and rarely even know all the individual components involved.

I though encourage people to think along Watto's lines along with others. We got to start somewhere.

 

[watto]

I know dudes, that's why I said it was an overimplification. But the basics are well described - one of the reasons I'm choosing to specialize in sleep medicine. Nothing beats good cat research repeated over and over again in the past thirty years.

 

[michaelrack]

That's an interesting statement. Care to elaborate?

Very little is known about the functions of various stages of sleep in humans. Part of the problem is that good studies are hard to do- especially in humans, but even in animals. Sure, you can polysomnographically monitor a man or rat and wake him up as he is going into REM, but then you are also getting significant sleep deprivation/disruption, and it's hard separate the effects of REM deprivation from sleep deprivation in general.

there is some interesting research looking at sleep and memory, both slow wave (stage 3) and REM seem to have some role.

As others have mentioned, how much an antidepressant suppresses REM doesn't lead to any well-documented functional daytime decrements.

There are some interesting theories out there about mechanisms of actions of antidepressants and the role of REM suppression.

Watto, I was interested in some of the same areas as you are when I chose to specialize in sleep; Although currently, my job is primarily sleep apnea.

 

[nuttyguy]

For a while I was taking Lexapro and Dexedrine. My depressive issues were from a combination of things, with one of the biggest being fatigue. Due to that fact I feel like Dexedrine alone was like an anti-depressant. The Psychiatrist who first prescribed commented on the two working well together and it seemed to turn out that way for me.

The Dexedrine was in the spansule form. From what I read this is essentially a timed release technology that's a little older. Sometimes taking past noon or so would make it hard to sleep in the evening.

I would have liked to have also tried some sleep medication, but my docs didn't like the idea of giving a stimulant and sleep med to counter-act it at night.