With this post, we continue our biweekly series on medications used to treat bipolar disorder and related symptoms. Over the past weeks, we covered several commonly used atypical antipsychotics, including Zyprexa (olanzapine), Risperdal (risperidone), and Seroquel (quetiapine). This week, we turn our attention to antidepressants, specifically the SSRI (Selective Serotonin Reuptake Inhibitor) variety. Medications in this class include:

• Prozac
• Zoloft
• Paxil
• Celexa
• Lexapro
• Luvox

Although each of these medications has unique properties and may be more or less effective in the treatment of a particular individual, they have similar profiles in terms of potential benefits and drawbacks:

• Potential benefits: Antidepressant, anti-anxiety, treatment of obsessive compulsive (OCD) and related disorders, often reduces irritability related to depression and anxiety
• Potential drawbacks: Insomnia, sedation, agitation or mania, suicide ideation, change in sexual function, nausea or diarrhea, weight gain

First released in 1987, Prozac (fluoxetine is the generic) is the “granddaddy” of the SSRI’s. It has a long history of use and a solid track record of safety and efficacy. It is often my first choice when we have decided to use an SSRI for depression and/or anxiety symptoms. On a practical level, it is easy to dose – there aren’t a lot of in-between dose changes to make, and it is generally quite well-tolerated. The biggest potential downside is that is takes longer to work. But it also stays in your system longer because it has a longer “half life” in the blood, so there tend to be few withdrawal effects from either missing a dose or stopping the medicine altogether. Depressive symptoms can recur when a person stops taking fluoxetine or any other SSRI, but that is not the same as withdrawal.

Although mania grabs all the headlines, the recurrent and severe depressive episodes experienced by people with bipolar disorder are typically the most devastating and dangerous of the cycles. Mania and hypomania don’t typically trigger a visit to the doctor, while depression will more likely generate help-seeking behaviors., This often means that antidepressants will be the first medications considered.

Unfortunately, if bipolar is involved, an antidepressant taken without the protection of a mood stabilizer can induce mania and worsen the course of the illness. Because of this, if you (or your doctor) have any suspicions that your depression is actually part of a bipolar disorder, , you and your doctor will discuss the possibility of taking a mood stabilizer first (preferably one that controls depression as well as mania, such as lithium or Lamictal). If the mood stabilizer controls the depression, you’re in luck. If not, antidepressants may be added to the mix, with less risk of “manic switching.”

Several recent studies have suggested that it is not clear whether antidepressants work very well in bipolar depression. If someone is placed on antidepressants for bipolar depression, it is not clear at all how long they should stay on these meds. Some studies have indicated that long-term use of antidepressants in bipolar disorder makes things worse. But none of these findings are iron clad, because the studies often don’t distinguish between Bipolar I and Bipolar II; people with Bipolar I may respond very differently to antidepressants than do people with Bipolar II. In everyday practice antidepressants are used frequently in people with Bipolar II but less often in people with clear Bipolar I.

How does an SSRI work?

Serotonin is a neurotransmitter – a chemical in the brain that carries signals between synapses (gaps between nerve endings or brain cells). Neurotransmitters are sort of like email, enabling cells inside the body to communicate with one another.

The human brain has many different neurotransmitters, each of which specializes in certain operations, including cognition, memory, physical movement, immunity, and mood. Serotonin helps regulate mood, anxiety, sleep/wake cycles, sexual behaviors, and other brain functions.

Neurotransmitters work by moving from one brain cell (neuron) to another – through a space called the synapse. After the transmitter is used by the second neuron, the first neuron sucks it back up and breaks it down. SSRIs prevent the first neuron from absorbing and breaking down serotonin after its use, thus increasing its concentration in the synapse between neurons. This increased level of serotonin lessens symptoms of depression and anxiety for many people, although how that actually happens is still not clear.

Typical Dose

Most people on Prozac take 20 to 80 mg once a day. Your doctor will work with you to determine an effective dosage.

Potential Side Effects

Like most medications in its class, Prozac can potentially cause any of several negative side effects. The most serious are the following:

• Increased suicidality in children or teens: Clearly there is an increased risk of suicide and suicidal thinking in people with bipolar and depression as a whole. A large review of studies done on children and adolescents who were treated with antidepressants showed that there was an increase in the risk that these children would develop suicidal thoughts, compared to children taking placebo. Even with the increased risk, the rate of this side effect remains very, very low. These medications are far more likely to decrease the risk of suicide than to increase it. Careful monitoring and communication with the prescriber, especially early on in treatment with SSRI’s is essential in reducing this risk as much as possible.
• Increased risk of mania: As mentioned earlier in this post, a person with bipolar disorder taking an antidepressant without the protection of a mood stabilizer appears to be at higher risk of shifting into mania or hypomania. While there is some indication that some antidepressants have less risk of manic switching, the risk remains present in all antidepressants. The rate of switching and the actual level of risk is not clear at this time – some researchers suspect it is very high and others feel it is actually much lower than is generally presumed.
• Agitation, increased anxiety, or worsening depression or other paradoxical effects: This is not the same as a true manic switch, and can occur in people with or without bipolar disorder who take SSRI’s. In a small group of people, these medicines seem to irritate the brain wiring rather than soothe it. This appears to be more common in children and adolescents, but can occur in a subset of adults as well. Close monitoring with your prescriber will be important in detecting this.
• Serotonin syndrome: When combined with medicines used to treat migraine headaches known triptans, such as sumatriptan (Imitrex), or other drugs that elevate brain levels of serotonin (including the illegal drug Ecstasy), a life-threatening condition called serotonin syndrome can occur. Symptoms include restlessness, hallucinations, loss of coordination, racing heart, increased body temperature, blood pressure fluctuations, overactive reflexes, diarrhea, nausea, vomiting, coma, and possibly death.
• Persistent pulmonary hypertension of the newborn (PPHN): There are studies showing that babies born to mothers who were taking SSRI’S in the third trimester of pregnancy have an increased likelihood of this condition. Babies born with PPHN have restricted blood flow through their heart and lungs, reducing the supply of oxygen to their bodies. This can make them very ill and increase their risk of death. If you’re pregnant or planning to become pregnant, consult with the doctor who’s managing your medications.

Other less serious side effects can include the following. (Note: Many of these side effects are transient and occur when first taking these medications but do not persist.)

• Sweating
• Sleepiness
• Insomnia
• Nausea
• Diarrhea
• Tremor
• Dry mouth
• Loss of strength
• Headache
• Weight loss or gain
• Dizziness
• Restlessness

Remember: Any antidepressant can take 2-3 weeks or even longer to become fully effective; it may take several weeks to work up to a therapeutic dose. This means that your depression may not lift for several weeks. I often tell patients that however they feel in the first two weeks is unlikely to be how they feel in a month – so if they are feeling some early side effects, hold on because they will likely get better. Patience is important in getting these medications to work, but if you have any concerns about how you are feeling, you should contact your doctor. You will most likely have a follow-up visit with your doctor within a month or less of starting the medications; this is a good time frame for checking in to see if benefits have started or if side effects have faded or persisted.

For more about Prozac, visit Eli Lilly’s Prozac page.

If you’ve taken any form of Prozac for bipolar depression or are a doctor who has prescribed it, please share your experiences, insights, and observations.

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