A small proportion (5-10%) of women experience significantly more disruptive psychological symptoms that can range from moderate to severe intensity that is recognized as Premenstrual Dysphoric Disorder (PMDD).  Individuals with PMDD present with more intense psychological symptoms of substantially depressed mood and irritability, along with mood lability, anxiety, anger, difficulty concentrating, and insomnia that are of such substantial intensity that they cause significant impairment in daily functioning at work and in social and interpersonal relationships.

Physiological symptoms associated with PMDD may include fluid retention (e.g., breast fullness and pain, swelling in extremities, decreased urine output; gastrointestinal symptoms (e.g., cramps, bloating, constipation, nausea, increased appetite); skin problems (e.g., acne, itching, worsening of chronic conditions); neurological symptoms (e.g., headache, fainting, dizziness, vision changes); and other somatic symptoms.

PMDD is distinguished from other psychiatric mood disorders by their temporal cyclic nature; patients have symptoms only during the luteal phase of the menstrual cycle and report normal mood during the follicular phase. On average, symptoms last 6 days and peak 2 days before menses.  Individuals experiencing this same constellation of symptoms persistently and not just exclusively in the two weeks before menses would, of course, need evaluation and treatment for other mood or psychiatric disorders, but an individual with a persisting mood disorder may also have a cyclic PMDD worsening of their symptoms.

Risk factors for PMDD include having a family history of PMS or PMDD, having a personal or family history of a mood disorder (e.g., major depressive episodes, chronic dysthymia, post-partum depression, anxiety and other mood disorders), and it is also associated with a history of trauma and abuse, cigarette smoking, and lower educational achievement.

Medical work up should include both a gynecological examination, as well as, evaluation to rule out other systemic illness such as thyroid conditions, anemia, perimenopause, menopause and other systemic illnesses. In patients who take oral contraceptive pills (OCPs), it is important to assess if symptoms are present and as severe even when they are not taking the OCPs, to eliminate the possibility that the symptoms are a side effect of the OCPs.

To help distinguish between PMDD and PMS, patients can keep a daily mood diary for a period of time to establish a pattern. The Daily Record of Severity of Problems ( https://www.aafp.org/afp/2011/1015/afp20111015p918-fig1.pdf  ) is a useful tool to log daily mood symptoms.

A variety of treatment options may ameliorate the psychological symptoms of PMDD. Most particularly, antidepressants that exclusively affect serotonergic transmission (citalopram, escitalopram, fluoxetine, paroxetine, sertraline) can be effective and may be used on an on-off schedule during the luteal phase only, as they have a rapid onset of action for the condition, as compared to their typical delayed onset of action when used for treating depressive illnesses.  Buspirone has been shown to be efficacious in the treatment of both premenstrual syndrome (PMS) and PMDD.

The use of combined oral contraception (estrogen and progestin) is common and more effective than either alone. Drospirenone/ethinyl estradiol is FDA-approved for PMDD. GnRH agonists have been found to be helpful but have problematic side effects, including medical menopause.

Calcium, magnesium and Vitamin B6 supplementation and judicious use of non-steroidal anti-inflammatory agents may also be of benefit.

Non-medication approaches that show some promise includes bright light therapy, exercise, and chaste berry supplements.  Avoiding sugar, salt, caffeine and alcohol are also recommended.

PMDD is a serious mental health concern that can lead to significant impairment for those affected. It is important to have the tools to assess for this disorder and offer appropriate treatment when indicated.

References:

• https://www.hopkinsmedicine.org/health/conditions-and-diseases/premenstrual-dysphoric-disorder-pmdd
• https://emedicine.medscape.com/article/293257-overview?ecd=ppc_google_rlsa-traf_mscp_emed_t1-psych_us

Prior to the inclusion of DMDD in the DSM, the default diagnosis often used was that of Bipolar Disorder– this given the broad range of symptoms that may present in that disorder, but the general consensus is that that practice was inappropriate as many of these children did not comfortably fit within the bipolar spectrum.   Although many were at risk for ongoing psychopathology, few would progress to have adult presentations of Bipolar Disorder with manic, hypomanic and depressive episodes.   Additionally, it was felt that many youth exposed to chronic childhood trauma, disruptive upbringings and experiencing underlying learning and/or subtle neurological impairments and delays would be better served by a diagnosis that more accurately described their symptom profiles.

Children with DMDD typically exhibit severe, recurrent temper outbursts that are grossly out of proportion in intensity or duration to the situation occurring several times per week. The temper outbursts have to be disproportionate and out of sync with the child’s developmental age and can include both verbal and physical aggression. Between these temper outbursts, children with DMDD typically also display a tendency toward having an irritable or angry mood and present with challenges in developing and maintaining healthy relationships with adults including their parents (or foster parents), peers, teachers and others involved in their care.   A DMDD diagnosis does require that symptoms be present most of the day, on most days occurring in multiple environments and with persistence of this profile over the course of many months to years.  Brief periods of irritable or disruptive behavioral symptomatology limited to one or only a limited number of interpersonal situational or relationships would typically not be viewed as meeting criteria.   The persistence of negative reactivity and easily aroused irritability in multiple settings with multiple others is the hallmark of this disorder.  Co-occurring attentional difficulties, impulse control problems and depressive and angry mood states are common in the disorder and co-morbidity with various disorders needs to be considered both in diagnostic efforts and these issues clearly need to be adequately addressed in treatment planning.

DSM criteria note that the onset of symptoms must be before age 10 but not younger than 6. It is thought that DMDD is more likely to occur in boys than girls. The prevalence is not yet known, but is expected to be in the 2-5% range.

Some comparisons of the symptom profiles in other childhood disorders are of note:

ADHD is a neurodevelopmental disorder characterized by impairing hyperactivity, impulsivity and inattention, but persistent irritability and out-of-proportion temper outbursts are not typically seen with uncomplicated ADHD. Children with DMDD can have some challenges with hyperactivity and impulsivity but the underlying irritability and angry mood symptoms are distinguishing features.

Children with ODD exhibit a pattern of anger-driven disobedience and defiant behavior toward authority figures. Clinically it is observed that ODD stems from learned behavior and/or parenting challenges, whereas DMDD seems to have a more complex process associated quite often with more substantial life and developmental disruptions consequent to exposure to toxic stress conditions. While some of the symptoms of ODD may overlap with the criteria for DMDD, the symptom severity threshold for a DMDD diagnosis is higher and it is typically seen as a more severe condition. Most children with DMDD also meet criteria for ODD but only about 15% of children with ODD might be considered to also meet criteria for DMDD.   In this context, it is recommended that children who meet the criteria for both ODD and DMDD should only be diagnosed with DMDD.

Children with full syndrome presentations of bipolar disorder can have symptoms that are similar to those with DMDD. The primary difference is that the mood symptoms seen in bipolar disorder are typically episodic and recurrent, which is not the case in DMDD where the symptoms are more persistent.  Overtly manic episodes with grandiosity and inflated moods that can occur in bipolar conditions are not typically seen in children with DMDD.  Additionally, children with bipolar disorder would most typically have distinct periods of severe depression interspersed with periods of more normative and euthymic mood states, whereas the DMDD affected child is more likely to have chronic dysthymia and irritable reactivity that persists over time.  A diagnosis of pediatric bipolar disorder should be substantiated by overt mood cycling and would often be supported by positive family history.

As noted earlier, it has been shown that children who present with chronic, rather than episodic, irritability, who may have previously been given a diagnosis of bipolar disorder for lack of a better fit, are at greater risk of developing depression and generalized anxiety rather than life-long bipolar disorder.

Treatment of youth presenting with DMDD profiles will typically require multimodal interventions to address the behavioral, emotional, interpersonal and environmental challenges associated with the disorder and not infrequently this will entail referral to higher levels of care and more intensive coordination of services.   Medications, including SSRIs, stimulants, alpha adrenergic agonists and, at times, the antipsychotic medications may be appropriate to help modulate and regulate mood, impulsivity, attention and aggressive symptomatology.  Trauma focused and supportive psychotherapies and organized behavioral modification regimens are often required.   As noted above, it is important to assess for co-morbid disorders, underlying factors and antecedents/triggers to help make an accurate diagnosis and develop an optimal treatment plan.

Reference:  Diagnostic and Statistical Manual of Mental Disorders, 5th Edition; 2013: American Psychiatric Association

Decreased appetite:
If your patient’s appetite decreases after taking ADHD medicine, advise the parent to give the morning dose after breakfast so that the youth will eat better in the morning. Also advise them to serve a large dinner in the evening when the medication is beginning to wear off. Have them keep healthy, high-calorie, protein snacks on hand for whenever a child asks for food, even if it is before bedtime. Discuss with parents that it is more important to monitor the child’s weight than his day-to-day appetite. Advise them to let you know if the child’s poor appetite lasts for a long period, and consider reducing the dose or stopping the drug on weekends or summer breaks to allow appetite and food intake to return to normal.

Stomach pain or upset:
Advise parents not to give the medication on an empty stomach. Taking the medication with or immediately after food can be helpful for this side effect.

Sleep problems:
Parents should set up a regular bedtime routine that includes calming activities, such as bathing or reading.  Makes sure that a long-acting stimulant is only given in the mornings, typically no later than 10am, and an afternoon dose of a short-acting stimulant should typically not be given later than 3pm. If the sleep disturbance persists, the provider could consider switching from a long-acting to a shorter-acting form or reducing the dose or stopping an afternoon dose.

Daytime drowsiness:
If a child is taking atomoxetine (Strattera) or guanfacine (Tenex/Intuniv) or clonidine (Catapres/Kapvay) and experiences daytime sleepiness, consider giving the medication at bedtime instead of in the morning.  The provider could also consider lowering the dose or dividing the dose and giving it twice a day. 

Rebounding effects:
When an ADHD medication wears off in the afternoon or evening, some children have a period of more ADHD symptoms or irritability and moodiness.  This is more common with the stimulant medications than the non-stimulant medications. To prevent this “rebounding” consider using a longer-lasting medication or prescribing a small dose of fast-acting stimulant later in the day.

Mood Changes:
Make sure the parents are keeping an eye out for changes in the child’s mood and anxiety.  Stimulant medications can negatively affect mood symptoms and anxiety. If that does occur, consider using a non-stimulant medication instead to address the ADHD symptoms.

Finally, it is often advisable to schedule medication initiation or dosage changes to occur on weekends when parents can better monitor for side effect emergence

It is our hope that this practical primer on addressing the common side effects for ADHD medications is helpful to address problems that may arise in the primary care office. And remember providers can contact is at SmartCare for real-time consultation on particular cases.

Mania and hypomania are mood states characterized by: elevated or irritable mood and a combination of symptoms such as increased energy, decreased need for sleep, irritability, feelings of inflated importance, excessive talkativeness (pressured speech), racing thoughts, exaggerated but poorly judged activities, and increased ‘pleasurable’ high risk behaviors. Mania or hypomania may also co-exist with depressive features in patients with bipolar profiles, so assessment may be challenging, but the presence of manic or hypomanic symptoms is a diagnostic key point. Input from relatives or others may be quite helpful in diagnostic assessment and treatment planning, as patients’ insight into their mood elevation may be impaired.

Levels of Care: When a patient presents with suspected manic or mixed affective symptoms, an early step in the process should include an evaluation as to the level of care needed. Assessment of the patient’s mood state, behavioral profile, and functionality are central to the triage and diagnostic process. Management options will range from acute referral for psychiatric care or prioritized referral for outpatient mental health care, but may also include primary care intervention to stabilize the patient’s symptoms while more intensive specialty care is being arranged. Medical evaluation of potential contributing factors will typically also be warranted as discussed further below.

Mania: In full blown manic states, patients typically present as pressured, intense and are often disorganized or showing restricted, hyper-focused interests. They often engage in harmful activities (e.g., reckless driving, substance use, sexual promiscuity) and may present with grandiose or even frankly delusional thinking, sometimes with psychotic symptoms such as hallucinations. Evaluation for both aggressive behaviors and suicidal tendencies needs to be undertaken and, most typically, referral for emergency psychiatric evaluation is warranted for stabilization and intensive treatment.

Hypomania: More subtle but still prominent changes in mood and behaviors are found in hypomanic states and deviations from a patient’s baseline personality is the central consideration to assess. Changes in sleep profile, an atypical sense of urgency about psychosocial issues, generalized psychological activation (rapid speech, internal thinking), and an altered level of judgment and insight about life activities are significant areas to note. A history of recurrent elevated mood episodes, not related to clear environmental stressors, may be diagnostically relevant.

Acute Stress Reactions: Differentiating manic symptoms from acute stress reactions to major life changes can be challenging as individuals’ responses to a variety of stressors (interpersonal problems, job crises, health problems, trauma exposure, etc.). Symptoms may include disruption in sleep, elevation of anxiety, and depressive mood and thought content. A central differentiating feature would be the absence of elevated mood and a coherence of the patient’s response to the stress.

Medical Concerns: Factors that may cause manic symptoms include medications such as antidepressants, which can trigger mania, as can stimulants and steroids (prescribed or used for body building). Recreational drug abuse or withdrawal may also trigger mania or mimic the symptoms, so obtaining a drug history and drug screen is recommended. Medical exam is important as manic symptoms may be mimicked in hyperthyroidism. A physical exam and a TSH level are indicated. Other medical differentials would include seizures or a stroke.

Primary Care Interventions: Recognition of the symptoms of mania and hypomania and review of the patient’s psychosocial functioning are first steps in PCP efforts. With a provisional diagnosis, medical evaluation and planning for appropriate referral are next steps.

When emergency referral is not needed, yet outpatient intervention is not readily available, efforts to manage disabling symptoms should be considered, typically focusing on sleep issues and psychomotor agitation. Typically, use of a sedating antipsychotic agent, such as quetiapine (Seroquel), or risperidone (Risperdal) in low to moderate dose range (Seroquel 50-100mg HS; Risperdal 1-2mg HS) could be considered as an initial intervention, with titration as indicated by patient response. Longer term treatments such as either lithium carbonate or an anticonvulsant mood stabilizer could also be considered as viable first line alternatives, but do require more lab monitoring (blood levels and LFTs with carbamazepine. Finally, short term use of a benzodiazepine might be considered for sleep and agitation.