In the past, I have been prescribed several types of SSRI(s) for depression. The doctor prescribed me Zoloft, Celexe(sp?), and Lexapro at different times. None of them seemed to work, in fact they seemed to have made my depression worse.

He then started me on Wellbutrin and it seemed to have worked a little better, and there were no sexual side effects. The only problem was that it seemed to have caused my blood pressure to rise and I was very irritable. So irritable in fact that my partner left me… Without going into the details, my doctor seemed to think that there was something else causing it, or my irritability was caused by my depression and my blood pressure went up because of it…

To make a long story short, I was visiting my GP one day and I told him everything that I had been going through. He prescribed me a newer medicine called Provigil. Sir, I could not believe the difference it made in my life. I was actually talking to people again, laughing, I guess I was almost normal again, or at least how I thought normal people would feel.

I felt so good that I made a profound decision to move out of state. Their were just too many bad memories in the old town.

Well, when I moved I got a new job and with it new insurance, and they refuse to cover Provigil. Needless to say, I have been off Provigil for almost a year now and my depression is definitely coming back…

I feel like a big failure now… I am going to make an appt. with a new doctor and I don’t know what to tell him. I definitely don’t want to go the route of SSRI’s again.. They just seem to make my depression worse… What should I tell him/her? Is there any medicine that insurance usually covers that is as good as Provigil?

Thank you in advance

Provigil (Modafinil), unfortunately, is HIDEOUSLY expensive. At drugstore.com, it costs $20 a tablet for the 200 mg tablet, and $14.33 for the 100 mg tablet. I don’t know why the drug company charges such a high rate for this useful medication. Even Viagra is a lot cheaper. I am waiting for Provigil to become generic. The patent expires on April 2015. The company that produces Provigil will try switching people’s attention to Nuvigil (derived from Provigil) as the newest model drug sometime around this year. Nuvigil’s patent expires in 2023. At $600 a month for the 200 mg tablet, I can see why health insurance companies don’t want to pay for Provigil. It is also a controlled substance making some physicians wary of using it and one cannot obtain it from a Canadian Drugstore.

Psychiatrists are generally aware of Provigil and its uses. Thus, rather than a general practitioner, I would see a psychiatrist if treatment with provigil is desired.

Provigil is a mild stimulant. Stimulants increase norepinephrine plus or minus dopamine. Provil does it very very mildly. This makes it have less of a tendency to cause inflammatory signaling from the immune system and adrenal dysregulation, which limits treatment with other stimulants in the treatment of depression.

If it is difficult to obtain Provigil, then perhaps low dose stimulants such as Focalin XR 5 mg once or twice a day can help. Focalin is the only extended-release stimulant which is fairly mild and is available in an extended-release form to help reduce excessive norepinephrine signaling, which gets people into trouble via side effects. Another option is to use Phentermine. Phentermine is also a stimulant that raises norepinephrine and dopamine. It has a half-life of 17 hours, and thus may last 1.5 days in effect. The key is to use a very low dose, otherwise the stress from increasing norepinephrine can cause many side effects – including weight gain, insomnia, anxiety, irritability, etc. A 37.5 mg tablet is very inexpensive and generic. It can be cut into 1/8th tablet doses and taken. If insomnia occurs, the dose is too high.

Wellbutrin (Bupropion) is a stimulant that primarily increases norepinephrine. It may increase dopamine but this is very short-lived as compensatory mechanisms reduce dopamine signaling in response to Wellbutrin. Increasing norepinephrine can cause irritability and high blood pressure. Wellbutrin increase norepinephrine more than Provigil. Provigil can also cause irritability and high blood pressure, though less often than Wellbutrin.

Depressed mood often involves loss of dopamine signaling. Ideally, the treatment of depression helps restore dopamine signaling. Serotonin Reuptake Inhibitors (SSRIs, like Lexapro, Zoloft, Celexa) first reduce stress/norepinephrine signaling by increasing serotonin signaling. But the increase in serotonin signaling simultaneously reduces dopamine signaling. This is why some people experience worsened depression on an SSRI. It may be useful to still take it, however, since downstream changes from reducing norepinephrine signaling – such as reduction in inflammatory signaling, improvement in thyroid signaling, improvement in adrenal function, may eventually restore dopamine signaling above the loss increasing serotonin signaling caused, thus reducing depression. However, since depression often involves multiple system problems, restoring dopamine signaling may be difficult if a person has other problems which an SSRI ultimately does not address – e.g. nutritional deficiencies, significant thyroid problems, etc.

The use of stimulants to treatment depression is well known in psychiatry. Stimulants are actually the first medications to have been used to treat depression.

Stimulants, however, have their downsides. The biggest question is how long can they last. Since they work, in part, by increasing norepinephrine signaling, they simultaneously have actions which worse toward worsening depression. For example, most people with depression already have elevated norepinephrine signaling. This is one reason they have insomnia, anxiety, irritability, etc. as part of depression. Increased norepinephrine signaling is a compensatory action by the body in many patients. Thus increasing it more – via a stimulant – may have at least a short term benefit. But the treatment works both ways – to both improve mood and to worsen mood. For example, norepinephrine increase insulin resistance and inflammation. This can catch up with a person over time to cause a crash – or return of depression. Thus, stimulants have their use. But I also prefer examining a patient for the underlying causes of depression – and often there are numerous contributing causes. The loss of dopamine signaling in depression is a consequence of these other factors.