Serotonin headaches

Serotonin is an important neurotransmitter, a local hormone in the gut, a component of the platelet clotting process, and is thought to play a role in migraine headache. Serotonin is also one of the mediators of the signs and symptoms of carcinoid syndrome, an unusual manifestation of carcinoid tumor, a neoplasm of enterochromaffin cells. In patients whose tumor is not operable, a serotonin antagonist may constitute a useful treatment. 

A compensatory vasodilation of the cerebral blood vessels may lead to an increase in intracranial pressure, which causes a severe headache. Serotonin (5-HT) has been implicated in the pathogenesis of migraine. 

SSRIs are well tolerated. Adverse effects for compounds in this class include nervousness, tremor, dizziness, headache, insomnia, sexual dysfunction, nausea, and diarrhea. In addition, the tricycHc antidepressant clomipramine (33), which is a potent nonselective serotonin reuptake inhibitor, is approved for treatment of obsessive—compulsive disorder. 

Venlafaxine (48) is a stmcturaHy novel phenylethylamine derivative that strongly inhibits both noradrenaline and serotonin reuptake. It lacks anticholinergic, antihistaminergic, and antiadrenergic side effects. As compared to placebo, most common adverse events are nausea, somnolence, dizziness, dry mouth, and sweating. Venlafaxine-treated patients also experienced more headaches and nausea, but less dry mouth, dizziness, and tremor than patients treated with comparator antidepressants. 

Tegaserod maleate (Zelnorm) is a partial serotonin (5-HT4) receptor agonist that causes an increase in peristaltic activity and intestinal secretion and moderation of visceral sensitivity. It increases the frequency of bowel movements and reduces abdominal discomfort, bloating, and straining. It is indicated for the treatment of patients younger than 65 years of age who experience chronic idiopathic constipation. The most common adverse effects include headache, abdominal pain, diarrhea, and nausea. 

The triptans are considered specific therapies in that they target the pathophysiology underlying migraine.33 They abort headache through beneficial effects on neuronal imbalances.11 Triptans inhibit neurotransmission in the trigeminal complex and activate serotonin lb/Id pathways that modulate nociception in the brain stem. They also decrease the release of vasoactive peptides leading to vascular reactivity and pain.34 Triptans are a welcome addition to the therapeutic armamentarium in that they are available in intranasal, subcutaneous, and oral... 

Treatment of aminoacidurias with a low-protein diet may influence brain chemistry. It should be emphasized that the treatment of the patient with an aminoaciduria may affect brain chemistry, perhaps in an adverse manner. Nearly all patients receive a low-protein diet. Indeed, undiagnosed patients sometimes avoid consumption of protein, which they feel intuitively can cause lethargy, headache, nausea and mental confusion. As dietary protein declines, the intake of carbohydrate frequently increases. The concomitant rise of endogenous insulin secretion favors an increase in the ratio of the concentration of blood tryptophan to that of other amino acids, thereby promoting the entry of tryptophan to the brain. The latter amino acid is precursor to brain serotonin, which tends to increase. This physiology is known to be operative in patients with urea cycle defects. 

Selective serotonin reuptake inhibitors are considered to be less effective than TCAs for migraine prophylaxis and should not be considered first- or second-line therapy. However, they may be beneficial when depression is a significant contributor to headache. Preliminary data suggest a possible benefit with venlafaxine. 

When starting a SSRI, the abrupt increase in serotonin may cause side effects. In the brain, the short-term effects include headache, sleep disturbance, nervousness, anxiety, and tremulousness. The digestive system effects include nausea, loose stools, decreased appetite, and indigestion. Most of these effects are mild and shortlived or can be managed with over-the-counter remedies. Nausea, for example, can be minimized by taking a SSRI after meals. These effects are also commonly seen with venlafaxine and duloxetine, atypical antidepressants that block serotonin reuptake like the SSRIs. 

Buspirone does not share any of the problematic benzodiazepine properties such as sedation, motor impairment, addiction, physical dependence, or withdrawal. The most common side effects of buspirone include dizziness, nausea, headache, fatigue, and dry mouth. Despite its activity in the serotonin system, buspirone is not associated with the sexual side effects that plague the SSRIs, SNRIs, MAOIs, and TCAs. 

Venlafaxine is a serotonin and noradrenaline re-uptake inhibitor indicated in depression and may be used in generalised anxiety disorder. Venlafaxine can cause diarrhoea and headache as side-effects. It does not cause blurred vision. 

Mechanism of Action A serotonin receptor agonist that binds selectively to vascular receptors, producing a vasoconstrictive effect on cranial blood vessels. Therapeutic Effect Produces relief of migraine headache. 

Mechanism of Action An ergotamine derivative and alpha-adrenergicblocker that directly stimulates vascular smooth muscle, resulting in peripheral and cerebral vasoconstriction. May also have antagonist effects on serotonin. Therapeutic Effect Suppresses vascular headaches. 

The selective serotonin reuptake inhibitors (SSRI) have been used in adults for a wide variety of disorders, including major depression, social anxiety (social phobia), generalized anxiety disorder (GAD), eating disorders, premenstrual dysphoric disorder (PMDD), post-traumatic stress disorder (PTSD), panic, obsessive-compulsive disorder (OCD), trichotillomania, and migraine headaches. Some of the specific SSRI agents have an approved indication in adults for some of these disorders, as reviewed later in this chapter. The SSRIs have also been tried in children and in adults for symptomatic treatment of pain syndromes, aggressive or irritable ( short fuse ) behavior, and for self-injurious and repetitive behaviors. This chapter will review general aspects of the SSRIs and discuss their approved indications in children and adolescents. 

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