Question: I’m a 48 yr. old female with bipolar II disorder and have been taking 300mg/day of Wellbutrin XL and .25mg of Xanax on an as needed basis for anxiety. My depression and anxiety have increased significantly the past few months due to stress from a job change, death of my mom and an “empty nest.” I’ve also been experiencing some peri-menopausal symptoms such as irregular periods and occasional night sweats.

My psychiatrist would like me to try hormone replacement therapy before making any changes in my meds. My ob-gyn would like me to try Cenestin. I’m very nervous about HRT and would rather try adjusting my present med dosages or changing to another anti-depressant. How do you feel about the effectiveness of HRT for treating depression/anxiety for those of us with bipolar disorder?

– Maureen

Answer: Irregular menses and night sweats in a 48 year old woman is very suggestive of perimenopause. Perimenopause is a period of usually 2-4 years where mood symptoms are common, more so than during menopause. Presumably, the depressive symptoms are related to dropping estrogen levels. Decreasing estrogen results in decreasing serotonin levels in the brain. Lowering serotonin levels doesn’t necessarily cause depression, but in a woman with previous depression or certain genetic vulnerabilities, depression does frequently occur. Another possible mechanism for estrogen benefit is that it stimulates cell growth in the rapid access memory brain (hippocampus).

In bipolar disorder mood changes are more often related to changes in hormones, seasons, steroids or effects of medication than to psychosocial stressors. Estrogen is often the most effective treatment in this situation. For some women this is the only treatment I have found to work. Cenestin, Premarin by mouth, or Estradiol by patch or cream is the best way to take it. Low doses are better to start (.3 Cenestin or Premarin or .025 Estradiol patch or cream). Occasionally, treatment results in hypomania. Wellbutrin can also cause hypomania in bipolar II. Most patients with bipolar disorder need to be on a mood stabilizer (see Best mood stabilizers).

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Question: If Effexor XR helps decrease the amount of serotonin and norepinephrine uptake in the case of GAD, then why does it feel like I am racing all the time?

– Ryan

Answer: Generalized Anxiety Disorder presumably is due to genetic vulnerability, personality traits, and stress. We know of one specific genetic variation that alters serotonin levels. Giving an anxious person meds that stimulate serotonin receptors or norepinephrine receptors (e.g., metabolite of Trazodone or Yohimbine) increases anxiety.

Giving Effexor, especially at higher doses, may initially worsen anxiety symptoms since it initially increases levels of serotonin and norepinephrine. But over a period of 2-3 weeks or more on Effexor, symptoms improve - presumably related to down regulation of both of these transmitters. 225 mg of Effexor usually works better than 150, and 150 works better than 75. At 225 effects on norepinephrine and serotonin are about equal. At 75 the effects are mostly on serotonin.

Some people with GAD do well on just an SSRI like Lexapro. You may be supersensitive to the norepinephrine effect of Effexor and would do better on Lexapro. Other possibilities include some bipolar gene that results in being overstimulated by an antidepressant.

Taking a benzodiazepine like Niravam might help with “racing.” Klonopin might be better if your thoughts are racing.

Anxiety symptoms can be associated with many conditions. Physiology of norepinephrine and serotonin are complicated, especially for serotonin, because there are more than 10 different types of serotonin receptors, any of which can be too high or low. Each of these transmitters also does different things in different areas of the brain.

In the future we will be able to better predict your medication response by looking at your specific genetic profile and other brain function parameters. For now, if you can’t find a dose of Effexor that helps without causing significant side effects, you need to phase off and try other meds. You may also need a reevaluation to look for other possible causes of your symptoms. The average person with a significant anxiety or mood disorder has a total of 3 different diagnoses. This phenomenon of frequent comorbidity is mostly due to the “blind men and the elephant” problem. We just don’t have the full picture yet of how the mind and brain work.

Question: I have bad stomach pain after taking a drug for a bladder condition. I was also on Prozac, Elavil and Lorazepam at the time, for bladder and depression issues. I stopped the Prozac because I wanted to take less drugs, because now I also have to take Prevacid. So, currently I am taking Prevacid, Lorazepam, and Elavil (lowest dose of each) Would cymbalta work for me for the stomach pain? The doctors are calling it nonulcer dyspepsia.

Answer: I’m not clear about whether you are still on a med for a bladder condition, but I’m presuming not. Meds that effect the bladder usually also have some effects on the stomach. I’m guessing that the bladder condition is interstitial cystitis, but there are several other possibilities.

Prozac can result in stomach spasms and pain, either when first starting it or when going off. Tapering Prozac more slowly would help if that was the case. Starting it back would initially help and then tapering at 1-2/week would be less likely to cause problems. Cymbalta has been found to help with pain of various types, but Elavil also helps by similar mechanisms. Increasing the dose of Elavil should be tried before adding Cymbalta, which shouldn’t be mixed with Elavil (i.e., Elavil would best be tapered off before adding Cymbalta).

Make sure you find out what was causing the stomach pain. Sometimes the cause remains unclear in which case you need to monitor any possible related symptoms or changes and be periodically reevaluated.