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Prazosin: The Best Medication for Comorbid PTSD? 

Why does prazosin appear to be the safest and most effective medication for select patients with comorbid PTSD? 

The way to treat anxiety in bipolar disorder is to treat the bipolar disorder. Anxiety is a synonym for distress, and nearly all mental disorders cause distress, except perhaps the classic, euphoric manias that lift the patient into a carefree state of bliss.

Some mood episodes are more anxiety-provoking than others, and at the top of the list are mixed states. Although anxiety does not appear in the criteria for mixed states, it is often created when 

 The International Society for Bipolar Disorders has even calculated the exact proportions for this troubling recipe. It takes only 1 manic symptom during a depression, or 2 depressive symptoms during a mania, to spark anxiety.

Mixed states tend to respond better to anticonvulsants and atypical antipsychotics than to lithium, which may be why anxiety predicts resistance to lithium in 

 There are, however, 2 exceptions to this rule: suicide and panic disorder. Both mixed states and anxiety raise the risk of suicide in bipolar disorder, and lithium 

 This preventative effect is independent of lithium’s mood benefits, so it is worth considering lithium in patients who are suicidal, even when it has a lower chance of reducing the core symptoms.

Although the classic lithium-responsive patient tends to have pure manias and hypomanias and no anxiety disorder comorbidities, a recent study identified panic disorder as a 

 Although anxiety is low in pure mania and hypomania, these patients are on high alert for threat, which is the essence of panic disorder. One study found that they had more phobias of panic sensations than patients in 

The next step in treating mixed states is to reduce antidepressants and anything else that contributes to manic symptoms (eg, drugs of abuse, steroids, and irregular circadian rhythms). Most patients who are in a mixed state have been on an antidepressant for a long time, and it can be difficult to tell if the drug is exacerbating the mixed presentation. Given these uncertainties, it is best to taper slowly, 

 Rapid discontinuation can trigger mania and other mood symptoms. The work is much like tapering a benzodiazepine. If the symptoms worsen, raise back the dose and slow down the taper.

In bipolar disorder, anxiety is a non-specific symptom with 

, including mood episodes, stress, and comorbid anxiety disorders. With so many different causes, can any mood stabilizer truly be said to be anxiolytic? Probably not, but we do have a few trials that may point the way when selecting a mood stabilizer for a patient with significant anxiety.

Among the anticonvulsants, valproate and lamotrigine improved anxiety in small controlled trials of 

 Valproate’s evidence here is more robust, and this medication also improved anxiety in patients who do not have bipolar disorder, perhaps because of its benzodiazepine-like 

 Lamotrigine may also treat obsessive compulsive disorder through glutamatergic effects, based on a small placebo controlled and several uncontrolled studies.

The atypical antipsychotics can also improve anxiety. Quetiapine and olanzapine reduced anxiety in large, randomized, placebo-controlled trials of patients with bipolar depression and non-specific anxiety (both were secondary analyses). The effect sizes were large enough to make them noticeable to the casual observer (

0.35 for olanzapine and 0.56 for quetiapine

 Quetiapine had similar anxiolytic effects in the 300 mg and 600 mg doses, and olanzapine had similar anxiolytic effects as monotherapy or when paired with fluoxetine.

These anxiolytic properties do not seem to extend to other atypical antipsychotics. Ziprasidone and risperidone both failed in placebo-controlled trials of bipolar disorder with anxiety, and risperidone actually worsened anxiety in a study of bipolar with comorbid panic disorder.

The unanswered question here is whether these medications were targeting anxiety directly or treating mild mixed states. Most of the patients had 1 to 2 manic symptoms along with their depression, judging from their average Young Mania Rating Scale of 5, and anxiety was higher as the 

 On the other hand, quetiapine has a large effect size in generalized anxiety disorder (GAD), suggesting 

 Quetiapine came close to FDA approval in GAD, but was held back because the FDA did not think this disorder was severe enough to warrant all the risks of an antipsychotic. That lesson applies to bipolar disorder as well. Quetiapine may be very effective for anxiety, but it should not be used in mild cases.

Anxiety may not offer a direct path to pharmacotherapy in bipolar disorder, but it does tell us something about the care of the patient. These patients are at greater risk for treatment dropout, adverse effects of medications, substance abuse, and suicide. Supportive psychotherapy, fast-acting treatment, and an extra phone call to make sure they are tolerating any new medication go a long way in these cases.

is the Mood Disorders Section Editor for 

 and the director of the Mood Treatment Center. He has written several books on mood disorders, most recently 

The author does not accept honoraria from pharmaceutical companies but receives royalties from PESI for 

Bipolar mixed states: an international society for bipolar disorders task force report of symptom structure, course of illness, and diagnosis.

2. Swann AC, Secunda SK, Katz MM, et al. 

Lithium treatment of mania: clinical characteristics, specificity of symptom change, and outcome.

Suicidal Behavior in Mood Disorders: Response to Pharmacological Treatment.

4. Nunes A, Ardau R, Berghöfer A, et al. 

Prediction of lithium response using clinical data.

5. Simon NM, Otto MW, Fischmann D, et al. 

Panic disorder and bipolar disorder: anxiety sensitivity as a potential mediator of panic during manic states.

Treating anxiety by discontinuing antidepressants: a case series.

Treating nonspecific anxiety and anxiety disorders in patients with bipolar disorder: A review.

Divalproex in the treatment of bipolar depression: a placebo-controlled study.

9. Sheehan DV, Harnett-Sheehan K, Hidalgo RB, et al. 

Randomized, placebo-controlled trial of quetiapine XR and divalproex ER monotherapies in the treatment of the anxious bipolar patient.

10. Bach DR, Korn CW, Vunder J, Bantel A. 

Effect of valproate and pregabalin on human anxiety-like behaviour in a randomised controlled trial.

Valproate (depakine-chrono) in the acute treatment of outpatients with generalized anxiety disorder without psychiatric comorbidity: randomized, double-blind placebo-controlled study.

12. Bruno A, Micò U, Pandolfo G, et al. 

Lamotrigine augmentation of serotonin reuptake inhibitors in treatment-resistant obsessive-compulsive disorder: a double-blind, placebo-controlled study

. J Psychopharmacol. 2012;26(11):1456-1462.

13. Lydiard RB, Culpepper L, Schiöler H, et al. 

Quetiapine monotherapy as treatment for anxiety symptoms in patients with bipolar depression: a pooled analysis of results from 2 double-blind, randomized, placebo-controlled studies.

14. Tohen M, Calabrese J, Vieta E, et al. 

Effect of comorbid anxiety on treatment response in bipolar depression.

15. Slee A, Nazareth I, Bondaronek P, Liu Y, Cheng Z, Freemantle N. 

Pharmacological treatments for generalised anxiety disorder: a systematic review and network meta-analysis.

Some mood episodes are more anxiety-provoking than others, and at the top of the list are mixed states.

How to Treat Anxiety in Bipolar Disorder

A quick primer on nomenclature, issues to consider, and switching.

Psychiatric Treatment: Side Effects Basics

 (PTSD) is often found to be a comorbidity in patients with bipolar disorder. In fact, sometimes it is the primary problem.

Irritable mood is a regular feature of PTSD. Triggers include events or thoughts related to the original trauma, which elicit an immediate adrenalized fight-or-flight response. Patients with PTSD will almost always 

 with sleep disturbance, including nightmares, disturbed awakenings without nightmare recollection, and night terrors observed by bed partners but not remembered.

 Although mania can present with irritable (rather than elevated) mood during manic episodes, the irritability in mania tends to occur when others disagree with the unrealistic plans or problematic behaviors of the individual with mania. In DSM-5 mania, the patient must present with 4 rather than 3 of the additional [hypo]manic symptoms during manic episodes if the mood is irritable.

The best medication for PTSD-related sleep disturbances, and perhaps other symptoms as well, is prazosin, which is an α-1 adrenergic antagonist antihypertensive agent. There have been 9 randomized, placebo-controlled trials of prazosin for PTSD, 6 of which have reported positive results. Some of these study 

 were strongly positive, with effect sizes compared with placebo in the neighborhood of 1.0 for all symptoms.

, which was published in 2018 and included 304 veterans from 13 medical centers, found no efficacy with prazosin.

 Doses were raised over 5 weeks, to up to 20 mg in men and 12 mg in women (higher than previous studies for the women). Some guidelines (including the latest Veterans Affairs PTSD practice guidelines) concluded that the medication had little value. The authors and others tried to explain these negative results, noting issues such as clinicians’ reluctance to refer very distressed and unstable patients to the study. If patients were receiving trazodone, they could not participate unless they were willing to stop taking it. Trazodone helps many patients with PTSD fall asleep, even if it has not demonstrated efficacy for staying asleep and preventing 

. Prazosin (a nonsedative), on the other hand, is not particularly helpful for initial insomnia. Prazosin had also been prescribed in study hospitals for many years, and perhaps the best patient candidates had already been treated.

This study made it clear that there are many patients who do not respond to prazosin and that research is needed to determine whether there are predictors of response.

Already we know that high blood pressure, which is a common medical comorbidity in PTSD, is a predictor.

 Raskind has termed these patients the “adrenergic subtype” of PTSD. In their 2013 study,

 which reported positive results overall, the authors found that patients with a baseline systolic blood pressure of 110 mm Hg or less did not respond to prazosin better than to placebo.

 Benefits rose sharply with each increase of baseline systolic blood pressure of 10 mm Hg.

Another predictor of poor response could be active drinking in patients who have an alcohol use disorder (AUD) and are actively drinking. Results of a 

 (N = 96) with comorbid AUD who were actively drinking during treatment with prazosin showed no efficacy for sleep or other PTSD symptoms. In another negative study, veterans (N= 20) with nightmares and mild to moderate suicidal ideation were given prazosin at night.

 Nightmares improved more with placebo than with prazosin, and there was no difference in suicidal ideation or daytime PTSD symptoms. Thus, it may be that suicidal ideation predicts poor response; a larger study is needed to better understand this link. Notably, among the 3 trials reporting negative results for prazosin, the only positive finding for prazosin was a lower rate of suicidal ideation in the prazosin group (8%) compared with placebo (15%) in the large 2018 study.

 However, this was a secondary outcome measure.

In an 8-week study comparing prazosin, hydroxyzine, and placebo in 100 patients with 

 associated with PTSD (28% women), investigators found prazosin was superior to both hydroxyzine and placebo in reducing nightmares and improving other measures of sleep quality.

 Hydroxyzine was also more effective than placebo on these measures in this study, which is the only controlled study of hydroxyzine in PTSD to date.

In conclusion, prazosin appears to be effective and perhaps the best medication for properly selected patients with PTSD, especially for their sleep disturbances. It might also address daytime symptoms, including irritability. Prazosin generally does not interact with medications for bipolar disorder. It is not particularly sedating, so another medication is often 

 to address initial insomnia. Hydroxyzine and trazodone are good options.

 Clinicians should be aware that there is a rare risk of priapism with prazosin, so, theoretically, there may be a greater than usual risk when combining trazodone and prazosin. Patients should be warned to pay attention to this possible side effect.

The effective doses of prazosin (after slow titration over several weeks) in the studies supporting its use clustered around a mean of 15 mg at bedtime for men and about half that for women. However, patient sensitivity to the medication is 

, with some patients only needing 1 mg and some needing and tolerating more than 20 mg.

 The highest dose mentioned in the literature was 45 mg at bedtime in a case report.

is associate professor of psychiatry, Harvard Medical School, and colead psychiatrist at the US Department of Veterans Affairs, National Telemental Health Center, Bipolar Disorders Telehealth Program, Brockton, Massachusetts. He also serves as a member of the Editorial Board of

. Dr Osser has no financial disclosures regarding this article

The Psychopharmacology Algorithm Project at the Harvard South Shore Program: an update on posttraumatic stress disorder

2. Germain A, Richardson R, Moul DE, et al. 

Placebo-controlled comparison of prazosin and cognitive-behavioral treatments for sleep disturbances in US military veterans

3. Raskind MA, Peterson K, Williams T, et al. A trial of prazosin for combat trauma PTSD with nightmares in active-duty soldiers returned from Iraq and Afghanistan. 

4. Ahmadpanah M, Sabzeiee P, Hosseini SM, et al. Comparing the effect of prazosin and hydroxyzine on sleep quality in patients suffering from posttraumatic stress disorder. 

5. Raskind MA, Peskind ER, Chow B, et al.

 Trial of prazosin for post-traumatic stress disorder in military veterans

6. Raskind MA, Millard SP, Petrie EC, et al. Higher pretreatment blood pressure is associated with greater posttraumatic stress disorder symptom reduction in soldiers treated with prazosin. 

7. Petrakis IL, Desai N, Gueorguieva R, et al. 

Prazosin for veterans with posttraumatic stress disorder and comorbid alcohol dependence: a clinical trial

8. McCall WV, Pillai A, Case D, et al. A pilot, randomized clinical trial of bedtime doses of prazosin versus placebo in suicidal posttraumatic stress disorder patients with nightmares. 

9. Koola MM, Varghese SP, Fawcett JA. High-dose prazosin for the treatment of post-traumatic stress disorder. 

Prazosin appears to be effective and perhaps the best medication for selected patients, including those with bipolar disorder.

Comorbid PTSD: Update on the Role of Prazosin

Patients with heart disease who take lamotrigine may be at increased risk for arrhythmias, according to a US Food and Drug Administration (FDA) review. The FDA promised further information once other medicines in the same drug class are evaluated for similar effects.

“Laboratory testing performed at therapeutically relevant concentrations has shown that lamotrigine can increase the risk of serious arrhythmias, which can be life-threatening in patients with clinically important structural or functional heart disorders,” the FDA warned.

Lamotrigine is a seizure treatment for patients aged 2 years and older as well as a maintenance treatment for patients with bipolar disorder. It has been approved and on the market for more than 25 years.

Reports of abnormal electrocardiographic (ECG) findings and other serious issues raised the alarm. The FDA then required the in vitro studies to further examine lamotrigine’s effect on the heart. Reported problems included chest pain, loss of consciousness, and cardiac arrest.

The challenge now is to determine whether the potential benefits of lamotrigine outweigh the risk of arrhythmias in each individual patient.

The FDA encourages medical professionals and patients alike to report adverse events and side effects associated with lamotrigine to the FDA’s MedWatch Safety Information and Adverse Event Reporting Program through the 

 or by calling 1-800-332-1088 to request a form.

1. US Food and Drug Administration. Studies show increased risk of heart rhythm problems with seizure and mental health medicine lamotrigine (Lamictal) in patients with heart disease. News release. March 31, 2021. 

https://www.fda.gov/drugs/studies-show-increased-risk-heart-rhythm-problems-seizure-and-mental-health-medicine-lamotrigine

Is this treatment for bipolar disorder risking patients’ heart health? 

FDA Warning: Bipolar Medication May Increase Risk for Arrhythmias

American Association for Geriatric Psychiatry

 virtual annual meeting, “Management of Geriatric Bipolar Disorder: A Case Series and Review of Current Evidence Based Treatment Guidelines,” Rana Jawish, MD, and colleague David Atkison, MD, noted the challenges of treating bipolar disorder (BD) in older patients and future possibilities for treatment.

“Compared to younger patients, older patients with bipolar disorder spend less time manic and more time depressed,” said Jawish.

A huge concern is misdiagnosis: 40% to 60% of patients with BD are misdiagnosed, often with major depressive disorder or borderline personality disorder. According to 

 Jawish reviewed, 28% of geriatric patients with a neurodegenerative disease received a psychiatric diagnosis, commonly depression.

It may be difficult to differentiate BD from depression in geriatric patients. Jawish stated these indicators might signify BD in patients with depression: family history of BD; early onset, like in early 20s; seasonality; numerous previous episodes; history of antidepressant-induced episodes, such as mania or hypomania; history of treatment-resistant depression; previous inpatient hospitalizations; and previous suicide attempts.

Also surprising, there is only 1 randomized controlled 

 in geriatric BD comparing lithium and divalproex for the treatment of mania and hypomania.

 Post-hoc analyses of mixed age trials suggest that medications effective in a younger cohort are effective for geriatric patients as well.

“Only one trial,” Jawish emphasized. “What works for everyone will work for the geriatric population with bipolar too.”

Another issue is late diagnosis. “Due to stigma about seeking mental health treatment, there could be a delay between a patient experiencing significant, distressing symptoms and presenting to care for a diagnosis,” said Atkinson.

With late diagnoses, many patients do not receive a formal diagnosis of BD until their 50s or 60s, an age range where the onset of neurodegenerative diseases is more common. BD might then be mistaken for frontal temporal dementia.

“This is an area that needs more studies,” said Atkinson.

Overall, in their synthesis of existing guidelines, geriatric principles, and case series observations, Jawish and Atkinson agreed that medications intended for general population use were also effective for geriatric populations.

1. Woolley JD, Khan BK, Murthy NK, et al. 

The diagnostic challenge of psychiatric symptoms in neurodegenerative disease: rates of and risk factors for prior psychiatric diagnosis in patients with early neurodegenerative disease

2. Young RC, Mulsant BH, Sajatovic M, et al. 

Geri-BD: A Randomized Double-Blind Controlled Trial of Lithium and Divalproex in the Treatment of Mania in Older Patients with Bipolar Disorder

Misdiagnosis and late diagnosis may be preventing older patients with bipolar disorder from getting proper care. 

Difficulties Diagnosing Geriatric Bipolar Disorder

While psychotropic medications for schizophrenia, bipolar disorder, and other psychiatric disorders can cause weight gain, patients can take small steps to improve their health.

15 Steps to Helping Psychiatric Patients Achieve and Maintain a Healthy Weight

Susan J. Noonan, MD, MPH, talks about the lead up to, and the process of inpatient care. 

is a physician consultant and Certified Peer Specialist in the Department of Psychiatry at McLean Hospital and the Massachusetts General Hospital. She is the author of four books and a blog on managing depression, most recently 

Helping Others With Depression: Words to Say, Things to Do (December 2020)

. Dr Noonan offers peer counseling to fellow patients, including physicians and other professionals, and can be confidentially reached through her website at 

What happens if a patient is too ill to manage at home?

The Ins and Outs of Inpatient Admission

When Amazon Prime decided to stream selected stories from the “Modern Love” column of 

, I was excited. I had been an avid reader of this section, where individuals reflect on the intricate nature of human relationships. The episode that struck me was “Take Me As I Am, Whoever I Am,” based on 

the essay written by Terri Cheney in 2008

 Then an entertainment lawyer, Terri wrote about her struggles with ultradian bipolar disorder, revealing how she hid her condition from her friends before ultimately going public.

In the television series, Terri is played by Anna Hathaway, the Oscar-winning actress who takes you through the roller coaster of bipolar highs and lows. The episode starts with Lexi (Hathaway) during her manic high at a supermarket. She sports loud makeup, sequins, and bright clothes. She is instantly drawn to a man named Jeff and lands herself a date with him that week. The scene breaks into a flash mob dance reminiscent of the movie 

The high does not last. As soon as Lexi reaches home, she abruptly sinks into depression and curls up in a fetal position, almost catatonic in her bed. While she does manage to wake herself up for the date, she appears slow, dysphoric, withdrawn, and unkempt, making Jeff wonder if she has a twin.

A few mornings later, she wakes up, euphoric again, to the sound of birds chirping and calls Jeff for another date. However, by the time he arrives that night, she has flipped again, going from dancing around her apartment to sobbing uncontrollably on the bathroom floor. When Jeff walks away, she decides that things need to change. She needs to give everyone a chance to know the real her.

The episode illustrated how the stigma of mental illness keeps people from getting the help they need. What was unique was the portrayal of a high-functioning lawyer with ultra-ultra rapid cycling (ultradian) bipolar disorder, an uncommon diagnosis for even psychiatrists to make or witness. Lexi almost had no baseline or a euthymic phase. As a portrayal of bipolar disorder, the episode has its strong and weak points. Hathaway’s portrayal of Lexi’s depression makes you feel empathetic. Crumpled on her bathroom floor in tears, hopeless and terrified, Lexi is a realistic portrayal of many patients’ experiences. Lexi’s mania, however, looks as glamorous as a Hollywood movie. She is super productive and euphoric with no impairment or mixed symptoms. Unfortunately, many patients will not be able to relate.

Pluses and minuses aside, it is heartening to think that viewers will see and sympathize with Lexi’s condition. Ultradian can be difficult to recognize, even for psychiatrists, and it can be a controversial 

 While 12% to 24% of patients with bipolar disorder experience rapid cycling (a total of 4 or more mood episodes in a year), ultradian is characterized by multiple episodes in a day. Some psychiatrists would prefer to classify it as a mixed state. Ultradian might also be mistaken for borderline personality disorder (BPD), but there are ways to distinguish the disorders. BPD mood cycling is closely tied to events in patients’ emotional lives, so it may appear random. In contrast, the underlying chemical disturbance in ultradian bipolar disorder will lead to more regular mood cycling.

Despite its rarity, ultradian has been on psychiatrists’ radar for decades, and good treatment options are available. Robert M. Post, MD, and colleagues first described 

 Anticonvulsants like valproic acid and carbamazepine might be more effective for treatment than lithium. It is also important to reduce triggering factors like antidepressants, drugs of abuse, thyroid abnormalities, and irregular sleep schedules. There are promising results on calcium channel blockers like 

In the final scene of the show, Lexi finally opens up about her condition to a coworker. It is a powerful moment in which she describes the cathartic experience as an elephant lifting its foot off her chest. After a trial of several medications and electroconvulsive therapy, she finds a new stability. She is ready to begin a new chapter in her life.

Cheney’s column and the episode end with 

: “I’ve finally accepted that there is no cure for the chemical imbalance in my brain, any more than there is a cure for love.”

is chief resident physician of psychiatry at the University of Missouri-Columbia.

1. Jones D. Coming out as bipolar in modern love and reliving it on TV. 

. October 18, 2019. Accessed February 15, 2021. 

https://www.nytimes.com/2019/10/18/style/anne-hathaway-modern-love-terri-cheney.html

2. Bauer M, Beaulieu S, Dunner DL, et al. Rapid cycling bipolar disorder—diagnostic concepts. 

3. Kramlinger KG, Post RM. Ultra-rapid and ultradian cycling in bipolar affective illness. 

Word of the day: ultradian cycling. Published July 4, 2020. Accessed February 15, 2021.

https://www.thecarlatreport.com/blog/word-of-the-day-ultradian-cycling/

5. Cheney T. Take me as I am, whoever I am. 

. January 13, 2008. Accessed February 15, 2021.

https://www.nytimes.com/2008/01/13/style/modern-love-take-me-as-i-am-whoever-i-am.html

A high-powered lawyer faces her toughest opponent yet: mental illness stigma.

Handling the Highs and Lows of Ultradian Bipolar Disorder—and Love 

Many patients with bipolar disorder (BD) have comorbid substance use disorders, including nicotine use. Some 

the chances of successfully addressing other substance use.

The mechanisms of nicotine and other substances are similar, so it is necessary to stop all substances that are maintaining the pathological processes. Patients, and some clinicians, erroneously believe it is OK to wait to address cigarette and other nicotine use.

The most effective smoking cessation medication is 

. The EAGLES study, a randomized, double-blind, placebo-controlled trial (N=8144) compared varenicline, bupropion, and nicotine replacement therapy (NRT). The results confirmed many smaller 

 that varenicline treatment had the best outcome (defined as abstinence at weeks 9-12).

 The investigators also studied the effects among various diagnoses by dividing patients into 2 equal cohorts—one with and the other without psychiatric disorders (70% unipolar and bipolar mood disorders, 20% anxiety disorders, and 10% psychotic disorders). The study found varenicline performed the best of the 4 treatments in both groups. In the nonpsychiatric cohort, abstinence rates were 38% for varenicline vs 26% on other active treatments and 14% on placebo. In the psychiatric cohort, abstinence occurred in 29% on varenicline, 19% to 20% on the other medications, and 11% on placebo.

The safety results may surprise some clinicians and patients. No differences were reported in moderate to severe neuropsychiatric adverse effects (eg, depression, suicidality, aggression) between varenicline and placebo in either cohort. In fact, as a result of the EAGLES findings, the US Food and Drug Administration removed the longstanding black box warning regarding such adverse effects. Interestingly, these neuropsychiatric adverse events can occur, but they are not more common if the patient is on varenicline. The effects are proposed to be due to 

 withdrawal. These safety results are consistent with many other studies, and the call to “stop ringing the alarm bell” was in the 

 Previous studies included patients with stabilized BD, and findings showed excellent efficacy and safety regarding precipitation of mood swings. There seem to be no significant drug interactions with any bipolar medications.

If smoking cessation fails on varenicline, controlled studies have shown augmentations with NRT or bupropion can add efficacy.

 Bupropion, however, is probably not a good choice for a patient with BD. The preferred augmentation would be NRT with patch and oral agents followed by slow taper; this strategy may blunt the nicotine withdrawal and increase success rates.

One minor adverse effect of varenicline is insomnia. 

 and disturbed awakenings associated with posttraumatic stress disorder (PTSD) may increase with varenicline. Before initiating varenicline, sleep disturbance associated with PTSD should be managed with prazosin. Five out of 8 placebo-controlled studies have found efficacy for prazosin. (Prazosin for PTSD in BD will be discussed in a future article; dosing and procedures with prazosin are best exemplified by Raskind et al.

 Prazosin may need to be increased if the nightmares resume or increase after starting varenicline.)

The hydrocarbons in cigarette smoke increase the activity of cytochrome P450 1A2, which metabolizes olanzapine and clozapine. Smoking cessation will, therefore, result in gradual deinduction of this enzyme, and plasma levels of these antipsychotics will increase over a week or 2.

is associate professor of psychiatry at Harvard Medical School and colead psychiatrist at the US Department of Veterans Affairs, National Telemental Health Center, Bipolar Disorders Telehealth Program, Brockton, Massachusetts.

A review of smoking cessation in bipolar disorder: implications for future research

A molecular basis for nicotine as a gateway drug.

3. Leão RM, Cruz FC, Vendruscolo LF, et al. 

Chronic nicotine activates stress/reward-related brain regions and facilitates the transition to compulsive alcohol drinking.

4. Anthenelli RM, Benowitz NL, West R, et al. 

Neuropsychiatric safety and efficacy of varenicline, bupropion, and nicotine patch in smokers with and without psychiatric disorders (EAGLES): a double-blind, randomised, placebo-controlled clinical trial

6. Rose JE, Behm FM. Combination treatment with varenicline and bupropion in an adaptive smoking cessation paradigm. 

7. Koegelenberg CF, Noor F, Bateman ED, et al. Efficacy of varenicline combined with nicotine replacement therapy vs varenicline alone for smoking cessation: a randomized clinical trial. 

8. Raskind MA, Peterson K, Williams T, et al. A trial of prazosin for combat trauma PTSD with nightmares in active-duty soldiers returned from Iraq and Afghanistan. 

Many patients with bipolar and other psychiatric disorders believe it is better to wait to address cigarette and other nicotine use. Here is why that is not necessarily the case.

Bipolar Disorder